Gene Regulation

Gene regulation is the process by which a cell determines which genes it will express, and at what time. Every cell in the organism contains a complete copy of that individual’s DNA, but gene regulation can turn that cell into a nerve cell or bone cell, depending on the genes expressed in response to regulation mechanisms. In addition to its role in cell differentiation, gene regulation also modulates cell function over its lifespan.

Product #

Description

Biochem/physiol Actions

Add to Cart

SML0949 4μ8C ≥98% (HPLC) 4μ8C is a potent inhibitor of the ER transmembrane protein IRE1, which mediates the unfolded protein response. 4μ8C inhibits regulated IRE1-dependent degradation (RIDD) and unconventional spicing of XBP1 mRNA in response to endopasmic reticulum (ER) stress, but has no affect on the kinase activity of IRE1.
SML0287 680C91 ≥98% (HPLC) 680C91 is a potent inhibitor of the enzyme tryptophan 2,3-dioxygenase (TDO), which directs the conversion of trypophan to kynurenin. Kynurenin has recently been identified as an endogenous lignd of the arylhydrocarbon receptor (AHR). TDO is highly expressed in glioma cells, and contributes to AHR-mediated glioma cell survival and suppression of anti-tumor immune responses.
SML0928 AD-01 trifluoroacetate salt ≥95% (HPLC) AD-01 is a potent antiangiogenic peptide a FKBPL fragment, which interact with cell-surface receptor CD44. AD-01 inhibits the self-renewal capacity of CD44-positive breast cancer stem cells (BCSC).
A1705 S-(5′-Adenosyl)-L-homocysteine Hydrolase from rabbit erythrocytes buffered aqueous glycerol solution, ≥10 units/mg protein (Lowry) Enzyme in vertebrates which catabolizes S-adenosyl-L-homocysteine.
SML1556 AEM1 ≥98% (HPLC) AEM1 is a potent inhibitor of deregulated Nrf2 transcriptional activity. AEM1 broadly decreases the expression of NRF2 controlled genes and sensitizes A549 cells to various chemotherapeutic agents.
SML0009 AI-1 ≥98% (HPLC) AI-1 promotes Nrf2 activation via the covalent modification of Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of Nrf2. Biochemical studies indicate that an aromatic chloride present within the AI-1 molecule undergoes a nucleophilic aromatic substitution reaction with cysteine thiols of Keap1.
A9232 AMI-1 sodium salt hydrate ≥98% (HPLC) Protein arginine N-methyltransferases (PRMTs) are involved in post-translational modification implicated in protein trafficking, signal transduction, and transcriptional regulation. AMI-1 does not inhibit lysine methyltransferase activity and does not interact with S-adenosylmethionine (AdoMet), unlike most methyltransferase inhibitors which compete for the AdoMet binding site. AMI-1 can modulate nuclear receptor-regulated transcription from estrogen and androgen response elements; and is a HIV-1 reverse transcriptase inhibitor. AMI-1 is a potent antagonist of NADPH-oxidase-derived superoxide production, but acts as a direct antioxidant rather than indirectly through methyltransferase inhibition.
A0987 n-Amyl 2-[3,5-dihydroxy-2-(1-nonanoyl)phenyl]acetate ≥98% (HPLC) n-Amyl 2-[3,5-dihydroxy-2-(1-nonanoyl)phenyl]acetate is a Nur77 agonist. Nur77 is a steroid orphan receptor that plays a critical role in regulating proliferation, differentiation and apoptosis. n-Amyl 2-[3,5-dihydroxy-2-(1-nonanoyl)phenyl]acetate, a cytosporone B analog, is a stronger activator of Nur77 than it parent compound. n-Amyl 2-[3,5-dihydroxy-2-(1-nonanoyl)phenyl]acetate treatment causes Nur77 migration to mitochondria, which results in mitochondrial Cyt c release into the cytoplasm and mitochondrial AIF redistribution in both the cytoplasm and nucleus.
SML0104 Ascochlorin ≥98% (HPLC), from Verticillium hemipterigenum Ascochlorin is an isoprenoid antibiotic produced by Verticillium hemipterigenum, initially identified as an antiviral and antitumor agent. Research also indicates that ascochlorin inhibits the Qi and Qo quinone binding sites of the mitochondria cytochrom bc1 complex. Moreover, ascochlorin activates p53, probably as a result of its inhibitory effect on mitochondrial respiration. In addition, ascochlorin has the ability to suppress the nuclear subscription enzyme protein-1, a nuclear transcription factor activator, which leads to suppression of the extra-cellular enzyme, matrix metalloproteinase-9 (MMP9). The regulation of MMP is implicated in renal development, macrophage differentiation, atherosclerosis, inflammation, rheumatoid arthritis, and tumor invasion. Ascochlorin was also found to be effective against Mx-1, an estrogen lacking breast cancer cell line.
A2385 5-Azacytidine ≥98% (HPLC) A potent growth inhibitor and cytotoxic agent; inhibits DNA methyltransferase, an important regulatory mechanism of gene expression, gene activation and silencing.
Causes DNA demethylation or hemi-demethylation, creating openings that allow transcription factors to bind to DNA and reactivate tumor suppressor genes.
A3656 5-Aza-2′-deoxycytidine ≥97% 5′-Azadeoxycytidine causes DNA demethylation or hemi-demethylation. DNA demethylation can regulate gene expression by "opening" the chromatin structure detectable as increased nuclease sensitivity. This remodeling of chromatin structure allows transcription factors to bind to the promoter regions, assembly of the transcription complex, and gene expression.
SML1419 B32B3 ≥95% (HPLC) B32B3 is a potent, selective and cell permeable VprBP inhibitor that suppresses xenograft tumor growth. B32B3 potently inhibits VprBP dependent formation of phosphorylated histone H2A on threonine 120 (H2AT120p).
B5556 Bay 11-7082 ≥98% (HPLC), powder Bay 11-7082 is an inhibitor of cytokine-induced IκB-α phosphorylation.
B5681 Bay 11-7085 ≥98% (HPLC), solid Inhibits NF-κB activated expression of ICAM-1, VCAM-1, E-selectin, IL-6 and IL-8.
SML1756 BAY-299 ≥98% (HPLC) BAY-299 is a potent and selective inhibitor of BRD1 and the second bromodomain of TAF1 (Transcription initiation factor TFIID subunits 1). BAY-299 is selective over other bromodomains including the other members of the BRPF family, and BRD9, ATAD2 and BRD4. BAY-364 is structurally similar to BAY-299 and serves as inactive control. For full characterization details, please visit the BAY-299 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1783 BAY-299N ≥98% (HPLC) BAY-299N (BAY-364) is structurally similar to selective BRD1/TAF1 inhibitor BAY-299 and serves as inactive control. BAY-299N is inactive against BRD1 and exhibit moderate activity against TAF1 (3 μM).
SML1276 BAZ2-ICR ≥98% (HPLC) BAZ2-ICR is a chemical probe for BAZ2A/B bromodomains with >100-fold selectivity over other bromodomains, with the exception of CECR2 (15-fold selectivity). BAZ2A is an essential component of the nucleolar remodeling complex (NoRC), which mediates recruitment of histone modifyine enzymes and DNA methylase involved in the silencing of ribosomal RNA transcription by RNA polymerase I. BAZ2B is believed to be involved in regulating nucleosome mobilization along linear DNA. BAZ2-ICR binds to BAZ2A with a KD of 109 nM (ITC) and to BAZ2B with a KD of 170 nM (ITC). BAZ2-ICR also shows accelerated Fluorescence recovery after photobleaching (FRAP) recovery at 1 μM in the BAZ2A FRAP assay. For full characterization details, please visit the BAZ2-ICR probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1272 I-BET762 ≥98% (HPLC) I-BET762 (GSK525762) is a selective inhibitor of bromodomain and extra terminal (BET) domain proteins BRD2, BRD3 and BRD4 with IC50 values of 32.5–42.5 nM and no interaction with other bromodomain-containing proteins. I-BET mimicks acetylated histone, preventing the protein-protein interaction between acetyl-lysines and the BET reader protein. This was shown to block expression of inflammatory genes in activated macrophages and confer protection against endotoxic shock and bacterial sepsis. I-BET762 also showed potent anti-myeloma activity in vitro and in vivo.
SML1655 BI-9564 ≥97% (HPLC) BI-9564 is a cell permeable, potent and specific inhibitor of BRD9 and BRD7. For full characterization details, please visit the BI-9564 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
B9061 Bicalutamide (CDX) ≥98% (HPLC), powder Bicalutamide (CDX) is a non-steriodal Androgen Receptor (AR) antagonist and a pure antiandrogen. It acts via balancing histone acetylation/deacetylation and recruitment of coregulators. Bicalutamide (CDX) abolishes androgen-mediated expression. For example, MMP13 upregulation in prostate cancer, PLZF (promyelocytic leukemia zinc finger protein), and GADD45γ (growth arrest and DNA damage inducible, gamma). Bicalutamide (CDX) is inhibited by non-genomic, transcription-independent stimulation of PI3K/AKT phosphorylation by androgens.
SML0528 BIM5078 ≥98% (HPLC) BIM5078 is a potent Hepatocyte nuclear factor 4a (HNF4a) antagonist that directly binds to ligand-binding pocket and modulates the expression of known HNF4a target genes. BIM5078 also inhibits insulin gene expression by disruption of E47 and PDX-1 binding to insulin promoter. BIM5078 is selectively cytotoxic to transformed cells.
SML1811 BIQ ≥98% (HPLC) BIQ (FG-2216) is an orally available and potent inhibitor of prolyl-hydroxylase (PHD). BIQ induces significant and reversible plasma erythropoietin (EPO) levels in vitro and in hemodialysis patients.
SML0959 Bis-1,4-(4-methoxybenzenesulfonamidyl)naphthalene ≥98% (HPLC) Bis-1,4-(4-methoxybenzenesulfonamidyl)naphthalene is a non-covalent inhibitor of the interaction between Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2). The Keap1–Nrf2 protein–protein interaction is considered a critical point of the Keap1–Nrf2–ARE (antioxidant response elements) system that protects cells from oxidative stress. Bis-1,4-(4-methoxybenzenesulfonamidyl)naphthalene prevents Keap1 repression of Nrf2 activation, allowing Nrf2 to initiate antioxidant response element (ARE) to protect the cell. Bis-1,4-(4-methoxybenzenesulfonamidyl)naphthalene has an IC50 of 2.7 micromolar and specifically binds to the Keap1 Kelch-DC domain.
SML1838 BNS ≥98% (HPLC) New BNS is a cell penetrant, potent and selective inhibitor of prolyl-hydroxylase 2 (PHD2). BNS regulates ~25% of hypoxia-regulated genes in MCF7 cells.
SML0560 BRACO19 hydrochloride ≥96% (HPLC) BRACO19 is a telomerase inhibitor that stabilizes G-quadruplexes, targeting telomeric G-quadruplexes, inducing DNA damage and cell-cycle arrest.
SML1346 BRD32048 ≥98% (HPLC) BRD32048 is a potent inhibitor of ETV1 (ETS variant 1) transcription factor oncoprotein. BRD32048 binds ETV1 directly, modulating both ETV1-mediated transcriptional activity and invasion of ETV1-driven cancer cells.
SML1706 BRD4354 ≥98% (HPLC) BRD4354 is a zinc chelating, reversible inhibitor of zinc-dependent histone deacetylases with selectivity for HDAC5 and HDAC9. BRD4354 has IC50 values of 0.85 μM and 1.88 μM for HDAC5 and HDAC9 respectively. Inhibition of other HDACs was lower, with IC50 values of 3.88-13.8 μM for HDACs 4, 6, 7, and 8 and over 40 μM for HDACs 1, 2, and 3. BRD4354′s mechanism is believed to involve zinc-catalyzed decomposition to an ortho-quinone methide, which covalently modifies nucleophilic cysteines within the proteins.
SML1080 BRD7116 ≥98% (HPLC) BRD7116 is a selective inhibitor of leukemia stem cells. BRD7116 had an EC50 of 200 nM for the leukemia stem cell (LSC)-enriched fraction of cells isolated from the bone marrow of leukemic animals in co-culture compared to ~50% inhibition at 20 μM against normal hematopoietic stem and progenitor cells (HSPCs) and AML cell lines. BRD7116 selectively targeted LSCe cells by cell-autonomous and cell-non-autonomous mechanisms. The exact mechanism is not known, but involved in impairing of the stroma’s ability to support leukemia cells, and inducing transcriptional changes consistent with myeloid differentiation.
B7563 BRD7389 ≥98% (HPLC) BRD7398 is a RSK kinase inhibitor that induces insulin expression and differentiation of pancreatic alpha into beta cells. BRD7398 inhibits RSK1, RSK2 and RSK3; IC50 values of 1.5, 2.4 and 1.2 uM, respectively. Treatment of mouse aTC1 cells with BRD7398 induced expression of b-cell markers Pdx1, Pax4, Iapp and Npy and also induced insulin production.
SML1262 BRD7552 ≥98% (HPLC) BRD7552 is a potent inducer of pancreatic and duodenal homeobox 1 (PDX1) transcription factor that enhanced insulin expression. BRD7552 upregulates PDX1 expression in both primary human islets and ductal cells. It appears that BRD7552 induce PDX1 expression through an epigenetic control.
SML1534 I-BRD9 ≥98% (HPLC) I-BRD9 is a selective cellular chemical probe for bromodomain-containing protein 9 (BRD9), thought to be a member of the chromatin remodelling SWI/SNF BAF complex, which plays a fundamental role in gene expression regulation. I-BRD9 has a pIC50 value of 7.3 with greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromodomain-containing protein 7 (BRD7) and greater than 70-fold selectivity against a panel of 34 bromodomains. For full characterization details, please visit the I-BRD9 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML0615 Br-DIF-1 ≥98% (HPLC) Br-DIF-1 is a bromine-substituted derivative of DIF-1 (differentiation-inducing factor-1). Br-DIF-1 significantly increases the efficiency of DMSO-induced differentiation of P19CL6 cells into beating cardiomyocytes by maintaing expression levels of the T-type calcium channel Cav3.1.
SML0992 Bromosporine ≥98% (HPLC) Bromodomains (BRDs) are protein-interaction modules that "read" ε-N-lysine acetylation motifs, such as those found in the N-terminal tails of histones. BRDs have been identified in chromatin-modifying enzymes (such as histone acetyltransferases (HATs)) as well as in transcription factors that regulate genes for cell cycle progression, signal transduction, apoptosis, and inflammation. Proteins containing bromodomains have been implicated in various diseases, such as cancers, inflammatory diseases and neurological diseases. Bromosporine is a broad spectrum BRD inhibitor. In HeLa cells, bromosporine accelerates FRAP recovery of BRD4 and CREBBP at 1μM. For full characterization details, please visit the Bromosporine probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
C8221 Caffeic acid phenethyl ester ≥97% (HPLC), powder Caffeic acid phenethyl ester is a specific inhibitor of the nuclear transcription factor NF-κB.
C4369 Calcipotriol hydrate ≥98% (HPLC) Calcipotriol, a synthetic derivative of calcitriol or Vitamin D, is used in the treatment of psoriasis and marketed under the trade name Dovonex. It has comparable affinity with calcitriol (Vit. D) for the Vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism. VDR belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. Binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation-related genes.
C0494 Cambinol ≥97% (HPLC), white powder Cambinol is a Sirtuin (Human Silent Information Regulator) Type 1/2 Inhibitor. Sirtuins are structurally and mechanistically unrelated to HDACs Class 1 & 2 deacetylases but share many protein targets. HDAC is a large complex enzyme family involved in epigenetic-control of gene expression. Sirt2 has an IC50 equal to 59 μM.
SML1176 Carboxypyridostatin trifluoroacetate salt ≥95% (HPLC) Carboxypyridostatin (carboxyPDS) selectively stabilizes RNA-containg G-quadruplex stuctures. Immunofluorescent staining of carboxyPDS treated cells using an anti G-quadruplex antibody reveals staining only in the cytoplasm and not the nucleus, demonstrating selectivity against DNA G-quadruplex structures.
SML0368 CHD-5 ≥98% (HPLC) CHD-5 is a potent aryl hydrocarbon receptor antagonist.
C1357 Cholecalciferol meets USP testing specifications Vitamin D acts through a receptor that is a member of the ligand-dependent transcription factor superfamily. Modulates the proliferation and differentiation of both normal and cancer cells. Has antiproliferative and antimetastatic effects on breast, colon, and prostate cancer cells. Activated vitamin D receptors in intestine and bone maintain calcium absorbance and homeostasis.
SML0698 CID 11210285 hydrochloride ≥98% (HPLC) CID 11210285 is a cell-permeable, potent and selective activator of Wnt signaling without inhibiting GSK-3β. CID 11210285is a Wnt agonist.
SML0375 CID 5951923 ≥98% (HPLC) CID 5951923 is an inhibitor of Kruppel-like factor 5 (KLF5) expression that significantly reduced endogenous KLF5 protein levels and decreased viability of several colorectal cancer cell lines. CID 5951923 is selective for colon cancer cells over nontransformed cells.
SML1798 10-Cl-BBQ ≥98% (HPLC) 10-Cl-BBQ is an orally bioavailable, non-toxic benzimidazoisoquinoline derivative that acts as an aryl hydrocarbon receptor (AhR) agonist via directly binding to AhR (IC50  = 2.6 nM in a competitive binding assay) and induces its nuclear translocation. 10-Cl-BBQ is shown to increase CD4+  T-cells that co-express CD25, CTLA-4 and ICOS, as well as several other genes associated with regulatory T cell (Treg) function in a graft versus host response model (GVH, C57BI/6 T cells injected into B6D2F1 host mice). 10-Cl-BBQ displays good pharmacokinetic profile in mice (t1/2 = 2 h, Cmax = 21.5 μg/L, 10 mg/kg, i.p.). Also shown to prevent insulitis in a NOD T1D mouse model which is independent of Fox3 +  Tregs (60 mg/kg, p.o, q.o.d.).
SML1063 CLEFMA ≥98% (HPLC) CLEFMA is a curcumin analog that elevates ROS levels and induces oxidative stress and apoptosis in lung cancer cell lines. CLEFMA inhibits tumor growth in lung cance xenografts.
SML0302 4-CMTB ≥98% (HPLC) 4-CMTB is a potent allosteric agonist of free fatty acid receptor 2 (FFA2).
SRP2073 N-CoR human recombinant, expressed in insect cells, ≥60% (SDS-PAGE) This gene encodes a protein that mediates ligand-independent transcription repression of thyroid-hormone and retinoic-acid receptors by promoting chromatin condensation and preventing access of the transcription machinery. It is part of a complex which also includes histone deacetylases and transcriptional regulators similar to the yeast protein Sin3p. This gene is located between the Charcot-Marie-Tooth and Smith-Magenis syndrome critical regions on chromosome 17. An alternatively spliced transcript variant has been described, but its full length sequence has not been determined
C9873 CPTH2 ≥98% (HPLC), powder CPTH2 is a histone acetyltransferase (HAT) inhibitor modulating the Gcn5 network. Histone Acetyltransferase (HAT) inhibitor modulating Gcn5 network. Histone acetyltransferases (HATs) act as transcriptional coactivators. Histone acetylation plays an important role in regulating the chromatin structure and is tightly regulated by two classes of enzyme, histone acetyltransferases (HAT) and histone deacetylases (HDAC). Deregulated HAT and HDAC activity plays a role in the development of a range of cancers. Consequently, inhibitors of these enzymes have potential as anticancer agents.
C2997 Cytosporone B ≥98% (HPLC) Cytosporone B (Csn-B) is the first naturally occurring agonist for nuclear orphan receptor Nur77. It binds with high affinity (IC50=0.278 nM) to the ligand-binding domain of Nur77 and stimulates Nur77-dependent activities.

Nur77 is a nuclear receptor/transcription factor. A physiological ligand for Nur77 is as yet unknown, but there is increasing interest in Nur77 because of its known activities. Translocation of Nur77 from the nucleus to mitochondria initiates cell apoptosis, making it a potential target for cancer treatment. Nur77 is also involved in glucose homeostasis; it induces genes involved in gluconeogenesis. Csn-B physically binds to Nur77 and activates its transactivational activity and translocation to mitochondria to induce apoptosis. It inhibits cancer cell proliferation and tumor growth.
Cytosporone B is a fungal metabolite closely related to phomposin C. It is the first known agonist for the nuclear orphan receptor Nur77. It binds with high affinity (IC50 = 0.278 nM) to the ligand-binding domain of Nur77 and stimulates Nur77-dependent activities.

Nur77 is a nuclear receptor/transcription factor with no known physiological ligand, but there is increasing interest in Nur77 because of its known activities. Translocation of Nur77 from the nucleus to mitochondria initiates apoptosis, making it a potential target for cancer chemotherapy. Nur77 also induces genes involved in gluconeogenesis. Csn-B activates the Nur77 translocation to mitochondria to induce apoptosis, inhibiting cancer cell proliferation and tumor growth.
SML0599 DIF-1 ≥98% (HPLC) DIF-1 (differentiation-inducing factor-1) is isolated from a Dictyostelium slime mold, and is used to inhibit proliferation/promote differentiation in various cell lines.
D9568 3,3′-Diindolylmethane ≥98% (HPLC) Acid-catalyzed reaction product of a phytochemical naturally found in Brassicaceae, indole-3-carbinol. It functions as an antitumor agent. This derivative can both directly stimulate apoptosis at relatively high concentrations and sensitize TRAIL-induced apoptosis in human cancer cells. DIM induces a G1 cell cycle arrest in human breast cancer MCF-7 cells by a mechanism that includes increased expression of p21. DIM is a strong mitochondrial H+-ATPase inhibitor. The function of DIM and its derivatives as a new plant growth promoter has been studied in an eco-friendly system.
SML1508 C-DIM12 ≥98% (HPLC) C-DIM12 is a potent and selective nuclear receptor Nurr1 (NR4A2) activator that activates Nurr1 in urothelial carcinoma cells and in pancreatic cells. C-DIM12 suppresses inflammatory signaling in microglia.
SML0079 DiMNF ≥98% (HPLC) DiMNF is a naphthoflavone derivative, selective aryl hydrocarbon receptor modulator (SAhRM). DiMNF is an AHR ligand that does not induce the expression of AHR dependent genes, such as CYP1A1, but inhibits the expression of cytokine-induced acute phase response proteins such as serum amyloid A and complement C3.
D7946 DIM-C-pPhOCH3 ≥98% (HPLC) DIM-C-pPhOCH3 is a Nerve Growth Factor-Induced Bα (NGFI-Bα, Nur77) agonist
SML1814 3,6-DMAD hydrochloride ≥98% (HPLC) New 3,6-DMAD is an acridine derivative that selectively suppresses ER stress- (300 nM Thapsigargin) induced HT1080 cellular XBP1 mRNA splicing (Eff. conc. 500 nM), but not eIF2a phosphorylation, by directly inhibiting IRE1? RNase (endoribonuclease) activity and disrupting IRE1α oligomerization. 3,6-DMAD is shown to exhibit anti-multiple myeloma efficacy in cultures in vitro (%survival/[3,6-DMAD]/cell line/24 h = 13%/4 M/RPMI 8226 and 8%/1 μM/MM1.R) and completely suppress the expansion of established RPMI 8226 tumor in mice in vivo when administered via intraperitoneal injection (10 mg/kg q.o.d.).
SML1874 DM-NOFD ≥98% (HPLC) New DM-NOFD is a cell penetrant, prodrug of NOFD a potent and selective inhibitor of an asparaginyl hydroxylase FIH (factor-inhibiting HIF). DM-NOFD efficiently reduces HIF1a CAD (C-terminal activating domain) hydroxylation in MCF-7 cells.
D0196 Doxercalciferol ≥98% (HPLC), solubility: >10 mg/mL in DMSO Doxercalciferol is a Vitamin D2 analogue, a Vitamin D Receptor Activator (VDRA). Doxercalciferol acts as a pro-hormone, needing 25-hydroxylation in the liver for bioactivation into 1α, 25-hydroxyvitamin D2. Pivotal studies in adults on dialysis have demonstrated control of secondary hyperparathyroidism that is superior to placebo therapy, without undue suppression of 1st IMA-PTH < 300 pg/mL, or occurrences of hypercalcemia. Doxercalciferol has been shown to be effective in controlling secondary hyperparathyroidism of adult patients with CKD stages 3-4.
Doxercalciferol is a vitamin D2 analog that acts as a pro-hormone, activated in the liver to 1α,25-dihydroxyvitamin D2. Despite its relatively low affinity for the vitamin D receptor (VDR) (before activation), it is effective at suppressing expression of the parathyroid hormone (PTH) gene, and appears to act through the VDR.
SML1765 DPBQ ≥98% (HPLC) DPBQ is a potent apoptosis inducer that is specific for high-ploidy cells. It appears that DPBQ induces expression and phosphorylation of p53 and this effect is specific to tetraploid cells.
SML1727 EB1089 ≥98% (HPLC) EB1089 is a Vitamin D analog 50 to 200 times more potent than Vitamin D in inhibiting growth and inducing differentiation with half the hypercalcemic activity. Studies have found EB1089 to be more potent than vitamin D in inhibiting growth and inducing differentiation of some cancer cell lines. EB1089 enhances radio sensitivity of H460 and A549 non-small cell lung cancer (NSCLC) cells.
SRP0253 4EBP1 Active human recombinant, expressed in E. coli, ≥70% (SDS-PAGE) E1F4EBP1 (eukaryotic translation initiation factor 4E binding protein 1) is involved in protein synthesis, cell growth and survival. In unphosphorylated form, it suppresses the translation initiation of capped mRNAs. On the other hand, in phosphorylated form, it increases translation initiation. Phosphorylation of E1F4EBP1 releases it from eIF4E (eukaryotic translation initiation factor 4E), thereby resulting in cap-dependent translation. E1F4EBP1 is also involved in tumorigenesis and the gene is overexpressed in various carcinomas. It is also a substrate for mTORC1 (mammalian target of rapamycin complex 1). In non-phosphorylated conditions, it interacts with p21 (cyclin-dependent kinase inhibitor) and enhances destabilization of p21.
E8409 EF-24 ≥98% (HPLC) EF-24 is a IKK inhibitor and curcumin analog. EF-24 is more potent and bioavailable than curcumin, with 10-fold greater potency in cell death induction. It is also more efficacious in anti-cancer screens and less toxic than Cisplatin. EF-24 inhibits HIF-1alpha posttranscriptional activity and induces microtubule stabilization, in contrast to Curcumin. EF-24 up-regulates PTEN expression via inhibition of ubiquitination. EF-24 induces cell death through direct inhibition of IkappaB kinase (IKK), resulting in suppression in NFκB activity.
SRP0255 eIF4E Active human recombinant, expressed in E. coli, ≥70% (SDS-PAGE) EIF4E (eukaryotic translation initiation factor 4E) is a part of eIF4F complex, which is responsible for the recruitment of ribosomes to the capped end of mRNAs during mRNA translation. It acts as the rate-limiting element in cap-dependent mRNA translation in eukaryotic cells. It promotes the translation of pro-oncogenic mRNAs, including vascular endothelial growth factor (VEGF), cyclin D3, and Mcl-1 (induced myeloid leukemia cell differentiation). Up-regulation of this protein is linked with various cancers, such as prostate cancer, breast cancer, and lymphoma. Studies show that this protein is overexpressed in melanoma cell lines and is linked with resistance to vemurafenib. Thus, it might have potential as a therapeutic target to suppress melanoma cell proliferation and abrogating vemurafenib resistance.
SML0149 3-Ethoxy-5,6-dibromosalicylaldehyde ≥95% (HPLC) 3-Ethoxy-5,6-dibromosalicylaldehyde is a non-competitive inhibitor of Inositol-requiring enzyme 1 (IRE1). It inhibits XBP-1 splicing induced pharmacologically in human cells. 3-Ethoxy-5,6-dibromosalicylaldehyde potently inhibits the endoribonuclease of IRE1 but does not inhibit RNases A, T1, or L.
SML1392 FDI-6 ≥98% (HPLC) FDI-6 is a potent and specific inhibitor of FOXM1 that blocks DNA binding. FDI-6 binds to FOXM1 protein and specifically downregulates FOXM1-activated genes.
SML1559 Furamidine dihydrochloride ≥98% (HPLC) Furamidine (DB75) binds to strings of AT base pair sequences in DNA′s minor groove. Furamidine was originally developed as an anti-parasitic compound for a variety of diseases including Chagas′ disease. Furamidine targets AT rich sequences in trypanosome kinetoplast minicircle DNA (kDNA), resulting in subsequent destruction of the kinetoplast and cell death. Furamidine has also been found to inihbit tyrosyl-DNA phosphodiesterase (Tdp1) and act as a selective protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC50 of 9.4μM.
SML0666 GSK1210151A ≥98% (HPLC) GSK1210151A (I-BET151) is an inhibitor of the BET (bromodomain and extra terminal domain protein) family of acetyl-lysine recognizing, chromatin ′adaptor′ proteins. GSK1210151A displaces BRD3 and BRD4, PAFc and SEC components from chromatin resulting in inhibition of transcription at key genes (BCL2, C-MYC and CDK6) involved in the initiation of mixed lineage leukemia (MLL). GSK1210151A (I-BET151) showed good efficacy in 2 MLL animal models.
SML0768 GSK2801 ≥98% (HPLC) GSK2801 is a potent inhibitor of the BAZ2 family of bromodomain containing proteins. BAZ2A is an essential component of the nucleolar remodeling complex (NoRC), which mediates recruitment of histone modifying enzymes and DNA methylase involved in the silencing of ribosomal RNA transcription. BAZ2B is believed to be involved in regulating nucleosome mobilization along linear DNA. For full characterization details, please visit the GSK2801 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1684 GSK2850163 ≥98% (HPLC) GSK2850163 is a highly selective inhibitor of inositol requiring enzyme-1 alpha (IRE1α) with dual activity: it inhibits IRE1α kinase activity with an IC50 value of 20 nM and RNase activity with an IC50 value of 200 nM. IRE1α is a dual serine/threonine-protein kinase/endoribonuclease with two enzymatic domains: a trans-autophosphorylation domain and and endoribonuclease (RNase) domain. When activated, usually in response to endoplasmic reticulum (ER) stress such as the unfolded protein response (UPR), IRE1α oligomerizes and activates mRNA splicing of adaptive XBP1 transcription factor, which upregulates ER chaperones and ER associated degradation (ERAD) genes that promote degradation of ER unfolded proteins and facilitate recovery from ER stress. However, if ER stress is too high or chronic, IRE1α is hyperactivated, increasing many ER mRNAs, resulting in apoptosis. GSK2850163 interacts with IRE1α catalytic residues Lys599 and Glu612, displacing the kinase activation loop to the inactive DFG-out conformation. The rearrangement of the kinase domain-dimer interface also results in the RNAse domains rotating away from each other, inhibiting the RNase activity.
G0673 GSK4112 ≥98% (HPLC) GSK4112 is a rev-erbα, (orphan nuclear receptor NR1D1) agonist, the first agent able to reset the circadian clock in a phase-dependent manner. Rev-erbα impacts the precision of the circadian clock by repressing target gene activities with the help of a nuclear receptor co-repressor complex (NCoR) and HDAC3. GSK4112 competes with heme (rev-erb′s natural ligand) and enhances co-repressor complex recruitment and thus, repression of transcription. suggests that pharmacological modulation through Rev-erb may provide new routes to treat metabolic diseases, especially disorders of adipogenesis regulated by rev-erba.
SML1234 HAMNO ≥98% (HPLC) HAMNO is a potent and selective inhibitor of replication protein A (RPA) interactions with proteins involved in the replication stress response. HAMNO binds the N-terminal domain of RPA70 and inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. HAMNO enhances DNA replication stress in cancer cells and slow tumor growth in vivo.
SML0883 HIF-2 Antagonist 2 ≥98% (HPLC) Hypoxia inducible transcription factors (HIF) control gene expression when oxygen availability is low and are associated with the onset and progression of a variety of cancers. They are heterodimers of an HIF-α (HIF-1α, HIF-2α also known as EPAS-1, or HIF-3α) and aryl hydrocarbon receptor nuclear translocator (ARNT, also known as HIF-β). N-(3-Chloro-5-fluoropheny
SML1260 HLM006474 ≥98% (HPLC) HLM006474 is a pan-E2F transcription factor inhibitor. E2F s part of the CDK/Rb/E2F pathway. When phosphorylated by CDKs, the tumor suppressor retinoblastoma protein (Rb) is inactivated, releasing E2Fs and allowing cell cycle progression. HLM006474 inhibited DNA-binding of all E2F complexes and down-regulated expression of E2F4 protein. HLM006474 induced apoptosis of A375 melanoma cells and synergized with paclitaxel in lung cancer cell lines.
H4014 25-Hydroxycholecalciferol ≥98% (HPLC) Ergocalciferol (vitamin D2) and 25-Hydroxycholecalciferol (vitamin D3) are the two form of vitamin D which are activated in vivo by hydroxylation. Vitamin D2 and D3 may be used in a wide range of studies to assess their effects on function such as immune function and calcium homeostasis.
SML1134 I-CBP112 ≥98% (HPLC) I-CBP112 is a selective inhibitor of the bromodomain-containing transcription factors CREBBP (CBP) and EP300 (IC50 = 0.142 and 0.625 μM, respectively). I-CBP112 has little activity against other bromodomains at concentrations up to 1 mM. For full characterization details, please see I-CBP112 on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1199 ID45 ≥98% (HPLC) ID45 is an activator of a PERK-Nrf2 ER stress pathway with antiviral activity against coxsackievirus B3 (CVB3), the primary cause of viral myocarditis. ID45 was found to result in host cell survival during CVB3 infection by allowing maintenance of high protein translation rates for host mRNAs and suppressing cap-independent translation initiation of CVB3 RNA. ID45 induced upregulation of Glucose related protein 78 (GRP78), an indication of ER stress, and activated PKR-like ER protein kinase (PERK) which in turn caused nuclear accumulation of response element Nrf2, leading to an increase in antioxidant response elements such as NQO1. NQO1 protects eukaryotic cap-dependent translation initiation factor eIF4GI from cleavage and degradation, facilitating cap-dependent translation initiation of host cellular mRNAs and suppressing cap-independent translation initiation of viral RNA.
SML0110 Ilicicolin F ≥98% (HPLC), from Verticillium hemipterigenum Ilicicolin F belongs to the ascochlorin family of molecules. Ascochlorin is an isoprenoid antibiotic produced by Verticillium hemipterigenum. Ascochlorin and its derivatives have an inhibitory effect on mitochondrial respiration by blocking the oxidation-reduction of cytochrome b through center N of the cytochrome bc1 complex. Ilicicolins have antiviral activity. They inhibit the growth of the tobacco mosaic virus, herpes simplex virus type-1(HSV-1) and newcastle disease virus.

Compounds of the ascochlorin family such as Ilicicolin F, C, D and H show a wide range of inhibitory effects on farnesyl protein transferase (FPTase) activity, and a significant inhibitory effect on the activity of testosterone-5α-reductase. Ilicicolin C and F have a moderate inhibitory activity toward the enzymes acetylcholinesterase (AChE) and β-glucuronidase and are active against Pseudomonas syringae with IC50 values of 28.5 μg/mL.

All isolated ascochlorin analogs exhibit significant antitumor and cytotoxic activities. Ascochlorin and its homologues are usable in treating and/or preventing diseases that can be relieved by the retinoid X receptor ligand-dependent signal transcriptional regulation (i.e. hypertension, cerebrovascular diseases, rheumatoid arthritis, autoimmune diseases, complication of diabetes, arteriosclerosis etc.). Moreover, they can inhibit denaturation and/or necrosis of pancreatic Langerhans islet β-cells and therefore can sustain insulin productivity.
PZ0331 ISOX-DUAL ≥98% (HPLC) ISOX-DUAL is a potent dual inhibitor of the bromodomain of CREB binding protein (CBP BRD) and bromodomain-containing protein 4 (BRD4).
PZ0332 ISOX-INACT ≥98% (HPLC) ISOX-INACT is an inactive control probe for the highly-selective inhibitor of the bromodomain of CREB binding protein (CBP BRD) PF-CBP1.
SML0974 (+/-)-JQ1 ≥98% (HPLC) The human BET family, which includes BRD2, BRD3, BRD4 and BRDT, play a role in regulation of gene transcription. (+/-)-JQ1 ((+/-)SGCBD01) is a selective BET bromodomain (BRD) inhibitor that inhibits Brd4 (Bromodomain-containing 4). Brd4 forms complexes with chromatin via two tandem bromodomains (BD1 and BD2) that bind to acetylated lysine residues in histones and Brd4 association with acetylated chromatin is believed to regulate the recruitment of elongation factor b and additional transcription factors to specific promoter regions. The nuclear protein in testis (NUT) gene is known to form fusions with Brd4 that create a potent oncogene, leading to rare, but highly lethal tumors referred to as NUT midline carcinomas (NMC). JQ1 inhibits recruitment and binding of Brd4 to TNFα and E-selectin promoter elements, and accelerates recovery time in FRAP (fluorescence recovery after photobleaching) assays using GFP-Brd4. Thus JQ1/SGCBD01 is a useful tool to study the role of Brd4 in transcriptional initiation. For full characterization details, please visit the SGCBD01/JQ1 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1525 (-)-JQ1 ≥95% (HPLC) SGC probe negative control. (-)-JQ1 is an inactive enantiomer of JQ1 that serves as a negative control. (-)-JQ1 shows no significant interaction with BRD1-4 or other bromodomains.
SML1524 (+)-JQ1 ≥98% (HPLC) (+)-JQ1 is a high affinity, potent and selective inhibitor of BET bromodomain proteins, including BRD2, BRD3, BRD4 and BRDT. (+)-JQ1 (also known as SGCBD01), the active enantiomer of (+/-)-JQ1 (catalog no. SML0974), inhibits Brd4 (bromodomain-containing 4), which forms complexes with chromatin via two tandem bromodomains (BD1 and BD2) that bind to acetylated lysine residues in histones and Brd4 association with acetylated chromatin is believed to regulate the recruitment of elongation factor b and additional transcription factors to specific promoter regions. The nuclear protein in testis (NUT) gene is known to form fusions with Brd4 that create a potent oncogene, leading to rare, but highly lethal tumors referred to as NUT midline carcinomas (NMC). (+)-JQ1 inhibits recruitment and binding of Brd4 to TNFa and E-selectin promoter elements, and accelerates recovery time in FRAP (fluorescence recovery after photobleaching) assays using GFP-Brd4. Thus (+)-JQ1 is a useful tool to study the role of Brd4 in transcriptional initiation. For characterization details of (+)-JQ1, please visit the JQ-1 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1922 K67 ≥98% (HPLC) New K67 is a specific inhibitor against the interaction between KEAP1 (Kelch-like ECH-associated protein 1) DC (double glycine repeat and C-terminal region) domain and S349-phosphorylated (human Ser349, mouse Ser351) KIR (Keap1-interacting region) of p62/SQSTM1, thereby preventing phospho-p62 from blocking KEAP1-DC and NRF2 (nuclear factor erythroid 2-related factor 2) DLGex motif association. K67 effectively inhibits the proliferation of HCC (hepatocellular carcinoma) cultures (by 59% of Huh7 cells post 72 h 50 μM K67 treatment) with high cellular p62 S351-phosphorylation by restoring KEAP1-driven NRF2 ubiquitination and degradation.
SML1412 KRIBB11 trifluoroacetate salt ≥98% (HPLC) KRIBB11 is an inhibitor of the transcription factor Heat Shock Factor 1 (HSF1) with an IC50 value of 1.2 μM. KRIBB11 blocks induction of HSF1 downstream target proteins such as HSP27 and HSP70 by impairing the recruitment of Positive Transcription Elongation Factor b (P-TEFb) to the HSF1 transcriptional complex, preventing HSF1-mediated gene expression KRIBB11 inhibits tumor growth in vivo and acts synergistically to increase apoptosis in cancer cells treated with the HSP90 inhibitors Geldanamycin and 17-AAG.
SML1362 L755507 ≥98% (HPLC) L755507 is a potent β3-adrenergic receptor partial agonist with an EC50 value of 0.43 nM for β3 receptors with over 440-fold selectivity for β3 compared to β1 and β2-adrenergic receptor binding. L755507 has been shown to enhance CRISPR-mediated homology-directed repair (HDR) efficiency in human induced pluripotent stem cells (iPSCs), increasing the efficiency of GFP insertion by 3-fold compared to control cells.
SML1557 LP99 ≥98% (HPLC) LP99 is a potent and selective bromodomain BRD9 and BRD7 inhibitor with a higher potency for BRD9 (Kd = 99 nM) than for BRD7 (Kd = 909 nM), and no inhibition for any of the 48 other BRDs tested. LP99 was shown to disrupt BRD7 and BRD9 binding to chromatin in cells. LP99 also inhibited interleukin 6 (IL-6) secretion, suggesting that BRD7/9 plays a role in the regulation of pro-inflammatory cytokine secretion. LP99 is not cell cytotoxic up to 25 μM. For full characterization details, please visit the LP99 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML0441 LUF6283 ≥95% (HPLC) LUF6283 is a partial agonist of the hydroxy-carboxylic acid receptor 2 (HCA2; GPR109A). LUF6283 binds HCA2 with a Ki value of 0.55 mM, and an intrinsic efficacy for agonist activity of 76% of the full agonist effect of niacin. The EC50 values for niacin and LUF6283 are 0.41 and 3.1 mM, respectively. LUF6283 effectively lowers plasma lipid levels, but does not induce cutaneous flushing as observed with niacin treatment.
M6682 Methoprene acid ≥98% (TLC)  
SML0661 ML216 ≥98% (HPLC) ML216 is a membrane permeable selective inhibitor of Bloom (BLM) helicase, a member of the RecQ DNA helicase family. Bloom’s syndrome, caused by a mutation in BLM, is associated with susceptibility to cancer, growth retardation, immunodeficiency, sunlight sensitivity, and fertility defects. ML216 is selective for BLM over other members of the RecQ family, especially in vivo, and appears to act at the BLM-nucleic acid substrate binding site, inhibiting DNA binding and blocking BLM′s helicase activity. ML216 could be useful in studies of tumor cells depending on the ALT (alternative lengthening of telomeres) mechanism for telomere maintenance rather than on telomerase, which are proposed to be susceptible to BLM inhibition.
SML1755 ML264 ≥98% (HPLC) ML264 is a potent and selective inhibitor of Kruppel-like factor 5 (KLF5) expression. ML264 potently inhibits proliferation of colorectal cancer cells in vitro through modifications of the cell-cycle profile.
SML1833 ML385 ≥98% (HPLC) ML385 inihbits the activity of the Nrf2 transcription factor by binding to Neh1, a CNC-bZIP domain that allows Nrf2 to heterodimerize with small Maf proteins, blocking NRF2 transcriptional activity. Much research has been done on activating Nrf2 because it induces cytoprotective antioxidant genes. However, some cancer cells may use Nrf2 similarly for their survival. Nrf2 is overexpressed in certain cancers such as non-small cell lung cancer (NSCLC) often due to loss of function mutations in KEAP1, which targets Nrf2 for proteasomal degradation. ML385 was found to have anti-tumor activity with specificity and selectivity for NSCLC cells with KEAP1 mutations.
N7032 NFAT Inhibitor >96% (HPLC), solid High-affinity calcineurin-binding peptide that inhibits NFAT (Nuclear Factor of Activated T cells) activation and NFAT-dependent expression of endogenous cytokine genes in T cells.
PZ0348 NI-42 ≥98% (HPLC) NI-42 is a biased potent small molecule inhibitor of the bromodomain of the BRPF (bromodomain and PHD finger-containing) proteins, which are scaffolding proteins that assemble histone acetyltransferase (HAT) complexes of the MYST transcriptional coactivator family. NI-42 has an IC50 value of of 7.9 nM and is suitable for cellular and in vivo studies.
SML1486 NI-57 ≥98% (HPLC) NI-57 is a selective and potent inhibitor of BRPF (Bromodomain and PHD Finger) family of proteins (BRPF1/2/3). NI-57 shows accelerated FRAP recovery at 1 μM in the BRPF2 FRAP assay preventing binding of full-length BRPF2 to chromatin. For full characterization details, please visit the NI-57 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML0944 NK-252 ≥98% (HPLC) NK-252 is a very potent, specific activator of the transcription factor Nrf2, which activates antioxidant-associated genes. NK-252 induces expression of an antioxidant response element promoter driven reporter gene, and protects Huh-7 liver cells against H202 induced cytotoxicity.
SML1601 NSC59984 ≥98% (HPLC) NSC59984 targets various mutant p53 to restore wild-type p53 pathway via the activation of p73 in cancer cells. NSC59984 depletes a gain of function (GOF p53 mutants. NSC59984 is not cytotoxic against normal cells.
SML1005 NSC 617145 ≥98% (HPLC) NSC 617145 is a potent and cell-permeable inhibitor of Werner syndrome helicase (WRN) that causes accumulation of double-strand breaks (DSB) and chromosomal abnormalities in cancer cells.
SML0046 NSC 668036 hydrate ≥98% (HPLC) NSC 668036 binds to the PDZ domain of the Wnt-pathway signaling molecule Disheveled (Dvl), blocking the binding and activation of Dvl by Frizzled. In Xenopus embryos, NSC 668036 inhibited Wnt3A-induced expression of the target gene Siamois and formation of secondary axes.
SML1803 NVS-CECR2-1 ≥98% (HPLC) NVS-CECR2-1 (NVS-1) is a potent and selective inhibitor of CECR2 (cat eye syndrome chromosome region, candidate 2) gene. CECR2 is duplicated in the human disorder cat eye syndrome, which includes defects of the eye, heart, anus, kidney, skeleton, face, and may include mild mental deficiency. CECR2 is involved in neurulation, the folding process that results in the transformation of the neural plate into the neural tube, and is also thought to play a role in DNA damage response. NVS-CECR2-1 (NVS-1) binds to CECR2 with high affinity. It has an IC50 value of 47 nM in Alpha screen and a KD of 80 nM in ITC. NVS-CECR2-1 showed no cross reactivity in a BRD panel of 48 targets or any major activity in kinase, protease and receptor panels. For full characterization details, please visit the NVS-CECR2-1 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1836 β-ODAP ≥98% (HPLC) New β-ODAP is a potent inhibitor of HIF-prolyl hydroxylase-2 (PHD-2) that induces HIF dependent HRE (hypoxia response element) in normoxic conditions. β-ODAP is an analog of glutamic acid present in Lathyrus sativus (grass pea) that activates AMPA receptors. β-ODAP causes neurolathyrism upon prolonged consumption of L. sativus seeds.
SML1184 OF-1 ≥98% (HPLC) OF-1 is a chemical probe for the bromodomains of the BRPF (BRomodomain and PHD Finger containing) family of scaffolding proteins (BRPF1, BRPF2, BRPF3) that assemble histone acetyltransferase (HAT) complexes of the MYST family members MOZ and MORF. The BRPF1 protein is the scaffold subunit of the MYST acetyltransferase complex, which plays a crucial roles in DNA repair, recombination and replication as well as transcription activation. OF-1 binds to BRPF1B with a Kd of 100 nM , to BRPF2 with a Kd of 500 nM and to BRPF3 with a Kd of 2.4 mM, and shows >100-fold selectivity against most other bromodomains. The closest off-target effects are against BRD4 (39-fold selectivity) and 50% inhibition of TIF1a at 20 μM. For full characterization details, please see OF-1 on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1303 Olinone ≥98% (HPLC) Olinone is a potent and selective inhibitor of BET (bromodomain and extraterminal domain) first bromodomain BrD1 that facilitates the progression of primary oligodendrocyte progenitors toward a differentiated phenotype.
O0516 Oncrasin-1 ≥98% (HPLC) Oncrasin-1 is a suppressor of RNA processing machinery. Oncrasin-1 induces aggregation of PKCL in the nuclei and is proapoptotic.
SML1605 OTX015 ≥98% (HPLC) OTX015 is a potent inhibitor of the BET bromodomain proteins 2, 3, and 4 (BRD2/3/4).
SML1470 PACA ≥98% (HPLC) PACA is a potentiator of NGF-induced neurite outgrowth that attenuates 6-hydroxydopamine (6-OHDA) neurotoxicity in dopaminergic PC12 cells. PACA induced the nuclear translocation of transcription factor Nrf2 and the expression of antioxidant heme oxygenase-1 (HO-1).
PZ0325 PF-CBP1 ≥98% (HPLC) CBP is a transcriptional coactivator. The protein is a link between the DNA-associated transcription factors and the RNA polymerase 2 complex. It also exhibits histone acetyltransferase activity.
PF-CBP1 is potent and highly-selective inhibitor of the bromodomain of CREB binding protein (CBP BRD) that down regulates targets of CBP in macrophages primary neurons. Also, PF-CBP1 significantly reduces levels of RGS4 mRNA levels in neurons.
SML0939 PFI-3 ≥98% (HPLC) SMARCA4 (SWI/SNF related, Matrix associated, Actin dependent Regulator of Chromatin, subfamily A, member 4) is a transcriptional activator and is a component of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. SMARC4 (also known as BRG1) and the related protein SMARCA2 (also known as BRM) contain a bromodomain that is structurally similar to the PolyBromo1 (PB1) 5 bromodomain. PFI-3 is a selective chemical probe for SMARCA bromodomains that inhibits SMARCA2, SMARCA4 and PB1(5) bromodomains. For full characterization details, please visit the PFI-3 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
PZ0307 PFI-4 ≥98% (HPLC) PFI-4 is an SGC chemical probe for the bromodomains of the BRPF (BRomodomain and PHD Finger containing) scaffolding protein BRPF1B. The BRPF proteins (BRPF1/2/3) assemble histone acetyltransferase (HAT) complexes of the MYST transcriptional coactivator family members MOZ and MORF. The BRPF1 protein is the scaffold subunit of the MYST acetyltransferase complex, which plays a crucial roles in DNA repair, recombination and replication as well as transcription activation. Mutations in MOZ, MORF, and BRPF1 have all been associated with cancer. BRPF1 exists in 2 different isoforms: BRPF1A and BRPF1B. PFI-4 specifically binds to BRPF1B with a Kd =13 nM as determined by ITC. It reduces recovery time in triple BRD cell construct in FRAP and is potent in cells with IC50 250nM, while showing no effect on BRPF1A. For full characterization details, please visit the PFI-4 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML0226 Pseudocantharidin C ≥98% (HPLC) Pseudocantharidin C stimulates PP2A activity up to two-fold without influencing PP1. PP2A activation by pseudocantharidin C changes phosphorylation of tra2-beta1 at position T33 and promotes the SMN2 pre-mRNA exon 7 inclusion.
SML1143 PTC-209 ≥98% (HPLC) PTC-209 inhibits the expression of the oncogene BMI-1 (B lymphoma Mo-MLV insertion region 1 homolog), which encodes a polycomb group RING finger protein involved in cell cycle. PTC-209 lowers the self-renewal properties of colorectal cancer-initiating cells (CICs) The compound inhibits tumor growth, and reduces the levels of CICs present in colon cancer tumor xenografts in mice.
SML0678 Pyridostatin trifluoroacetate salt ≥98% (HPLC) Pyridostatin stabilizes G-quadruplexes, targeting the proto-oncogene SRC and telomeric G-quadruplexes, inducing DNA damage and cell-cycle arrest.
SRP0190 RbAp48 Active human recombinant, expressed in baculovirus infected insect cells, ≥40% (SDS-PAGE)  
R1906 RETRA ≥98% (HPLC), solid RETRA is a mutant p53-dependent activator of p73, an activator of p53-regulated genes, and a suppressor of mutant p53-bearing tumor cells. Greater than 50% of tumors express mutant p53 which is defective for the tumor-suppressor function and contributes to malignancy by blocking a p53 family member p73. Activation of p73 in human cancer produces a cytotoxic effect. RETRA increases expression level of p73 and releases p73 from the inhibitory complex with mutant 53. It thereby produces tumor-supressor effect, in vitro and in vivo, similar to functional reactivation of p53.
SML1685 Ribocil-C ≥98% (HPLC) Ribocil-C is a potent inhibitor of bacterial riboflavin riboswitches. Riboswitches are cis regulatory elements present in non-coding RNA that specifically bind to natural ligands to regulate gene expression. Ribocil-C blocks the flavin mononucleotide riboswitch-mediated expression of the ribB gene, which is required for riboflavin biosynthesis, with an IC50 value of 23 nM. Ribocil-C inhibited bacterial cell growth of E. coli MB5746 and bacterial burden in a mouse E. coli septicaemia model of infection.
SML1583 Roseoflavin ≥95% (HPLC) Roseoflavin is an analog of flavin mononucleotide (FMN) and riboflavin with antimicrobial activity. Roseoflavin is converted to the flavin mononucleotide (FMN) analog roseoflavin mononucleotide (RoFMN) by flavokinase and to the flavin adenine dinucleotide (FAD) analog roseoflavin adenine dinucleotide (RoFAD) by FAD synthetase, and acts as a riboflavin antagonist. Roseoflavin is an inhibitor of bacterial riboflavin riboswitches, cis regulatory elements present in non-coding RNA that specifically bind to natural ligands to regulate gene expression. Roseoflavin, converted to RoFMN, blocks the flavin mononucleotide riboswitch-mediated expression of the ribB gene, which is required for riboflavin biosynthesis.
SML0858 SC-1 ≥98% (HPLC) SC-1 is a derivative of the multiple tyrosine kinase inhibitor sorafenib with no kinase-inhibition activity. SC-1 blocks STAT3 phosphorylation and activation with similar potency to sorafenib, and induces apoptosis in hepatocellular carcinoma cell lines.
SML1133 SGC-CBP30 ≥98% (HPLC) SGC-CBP30 is a selective inhibitor of the bromodomain-containing transcription factors CREBBP (CBP) and EP300 (IC50 = 0.021 and 0.038 μM, respectively). SGC-CBP30 has little activity against other bromodomains at concentrations up to 1 mM. For full characterization details, please visit the SGC-CBP30 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML0880 Shz-1 ≥98% (HPLC) Shz-1 is an enhancer of myocardial regenerative repair by stem cells. Shz-1 specifically activates Nkx2.5, one of the earliest lineage-restricted genes to be expressed in cardiovascular progenitor cells and improves iPSC-derived cardiac differentiation. Shz-pretreated human mobilized peripheral blood mononuclear cells (PBMCs) injected in a rodent model of myocardial infarction enhanced engraftment of the cells and improved cardiac function.
SML1762 SI-2 ≥98% (HPLC) SI-2 targets the receptor-interacting domain (RID) of steroid receptor coactivators (SRCs) and suppresses cellular transcriptional activity (Effec. conc. >/= 5 nM in cell-based SRC-1, SRC-2, and SRC-3 reporter assays) by downregulating SRCs protein, but not transcript level (Effec. conc. >/= 12.5 nM against SRC-3, >/= 25 nM against SRC-1 and SCR-2 in MDA-MB-468 culture). SI-2 is cytotoxic to breast cancer cultures (IC50 = 1.5 nM/BT-474, 3.4 nM/MDA-MB-468, 22 nM/MCF-7), but not to normal hepatocytes even at 500 nM concentration. SI-2 is reported to be orally available in mice and, when administered intraperitoneally (2 mg/kg b.i.d.), effectively suppress MDA-MB-468-derived tumor expansion in mice in vivowith good pharmacokinetics (Cmax = 30 μM, tmax = 0.25 h, t1/2 = 1.0 h; 20 mg/kg i.p.) and no apparent adverse effects to the animals.
SML1518 SID 3712249 ≥95% (HPLC) SID 3712249 (MiR-544 Inhibitor 1) is an inhibitor of the biogenesis of microRNA-544 (miR-544). MiR-544 represses expression of mTOR, promoting tumor cell survival in a hypoxic environment. Inhibition of miR-544 processing with MiR-544 Inhibitor 1 caused apoptosis in triple negative breast cancer cells in response to hypoxic stress, sensitized their response to 5-fluorouracil, and blocked their growth after transplantion into immunodeficient mice. SID 3712249 (MiR-544 Inhibitor 1) is believed to bind directly to the precursor miRNA, blocking production of the mature microRNA and resulting in decreased miR-544, HIF-1α, and ATM transcripts. MiR-544 Inhibitor 1 was as selective and 25-fold more potent than a 2′-O-methyl RNA antagomir.
S1323 SID7969543 ≥98% (HPLC), solid SID7969543 is a SF-1 (or NR5A1) inhibitor. The Steroidogenic Factor 1 (SF-1, also known as NR5A1) is a transcription factor belonging to the nuclear receptor superfamily. It plays a central role in sex determination and the formation of steroidogenic tissues during development, and is involved in endocrine function throughout life. It has also been reported to have a potential role in obesity. It has also been observed that an increased concentration of SF-1 causes adrenocortical cell proliferation and cancer.
S8559 Sinefungin 95% (HPLC), powder Sinefungin blocks the methylation of bases in DNA and RNA, such as 5-methylcytosine or N6-methyladenosine, suggesting a role in gene expression. In addition, sinefugin is involved in physiological processes such as aging and carcinogenesis.
Sinefungin blocks the methylation of bases in DNA and RNA, such as 5-methylcytosine or N6-methyladenosine, suggesting a role in gene expression. In addition, sinefugin is involved in physiological processes such as aging and carcinogenesis.
Methylation inhibition by sinefugin is often accompanied by an altered rate of cytosine deamination that is coupled to transition mutation in the DNA. Sinefugin inhibits Epstein-Barr viral activity and this inhibition is related to the change in DNA methylation and gene expression. It can cause a rate change in several restriction DNA endonuclease activities, including Mme I, which is not connected to the inhibition of the methytransferase activity.
SRP0476 SMARCA2 (1375-1511) human recombinant, expressed in E. coli, ≥90% (SDS-PAGE)  
SML1471 SN50 trifluoroacetate salt ≥95% (HPLC) SN50 is an NF-KB cell permeable inhibitory peptide. The SN50 sequence contains the nuclear localization sequence (NLS residues 360-369) of the transcription factor NF-KB p50 linked to a peptide cell-permeabilization sequence, the hydrophobic region (h-region) of the signal peptide of Kaposi fibroblast growth factor (K-FGF). SN50 Peptide inhibits translocation of the NF-KB active complex into the nucleus.
SML0464 SPA0355 ≥98% (HPLC) SPA0355 inhibits cytokine and LPS-induced activation of NF-kB in cell-based assays, blocking IKK-2 phosphorylation, degradation, and p65 binding to DNA. In vivo, SPA0355 inhibits paw edema and joint destruction in a mouse collagen induced arthritis model.
SML1513 SR1848 ≥98% (HPLC) SR1848 is a cell penetrant and potent inhibitor of orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) that reduces the expression of CyclinD1 and E1, which results in inhibition of cell proliferation. SR1848 induces rapid translocation of nuclear LRH-1 to the cytoplasm.
S9576 SR8278 ≥98%, semisolid SR8278 is a Nuclear Heme Receptor REV-ERB antagonist. REV-ERBα plays a critical role in regulation of the circadian rhythm by repressing target gene activities. Additionally, REV-ERBα has been shown to regulate metabolic processes including lipid and glucose metabolism. SR8278 blocks the ability of the synthetic agonist GSK4112 to enhance REV-ERBα-dependent repression and stimulates the expression of REV-ERBα target genes involved in gluconeogenesis.
SML0409 STF-083010 ≥98% (HPLC) STF-083010 is a potent inhibitor of the ER transmembrane protein IRE1, which mediates the unfolded protein response. STF-083010 inhibits IRE1 endonuclease and mRNA splicing activity in response to endopasmic reticulum (ER) stress, but has no affect on the kinase activity of IRE1.
SRP0475 TAF1 (1519-1651) human recombinant, expressed in E. coli, ≥90% (SDS-PAGE)  
SRP0470 TAF1L (1398-1516) GST tag human recombinant, expressed in E. coli, ≥82% (SDS-PAGE)  
SRP0468 TAF1L (1398-1516) His tag human recombinant, expressed in E. coli, ≥90% (SDS-PAGE)  
SRP0472 TAF1L (1398-1649) GST tag human recombinant, expressed in E. coli, ≥80% (SDS-PAGE)  
SRP0471 TAF1L (1517-1649) GST tag human recombinant, expressed in E. coli, ≥89% (SDS-PAGE)  
SRP0469 TAF1L (1517-1649) His tag human recombinant, expressed in E. coli, ≥79% (SDS-PAGE)  
SML0834 2,3,5,4′-Tetrahydroxystilbene 2-O-β-D-glucoside ≥98% (HPLC) 2,3,5,4′-Tetrahydroxystilbene 2-O-β-D-glucoside induces the expression and enhances the activity of EPO. The compound stimulates mitochondrial biogenesis, and expression of hemoglobin in non-hematopoietic cells. 2,3,5,4′-Tetrahydroxystilbene 2-O-β-D-glucoside has demonstrated protective effects in cardiovascular disease and ischemia models.
SML1548 THPN ≥98% (HPLC) THPN is potent nuclear receptor TR3 (Nur77) antagonist that induces autophagic cell death in melanoma. Co-application of THPN with Akt2 inhibitors significantly represses tumor growth in xenograft mouse model.
SML0923 TIC10 ≥98% (HPLC) TIC10 is a potent blood brain barrier penetrant and orally active inducer of TRAIL production that induces death of multiple human cancers. TIC10 inactivates both Akt and ERK, which results in Foxo3a nuclear factor migration to the nucleus and binding to TRAIL promoter.
SML1068 TIC10 angular ≥98% (HPLC) TIC10 angular is a potent blood brain barrier penetrant and orally active inducer of TRAIL production that induces death of multiple human cancers. TIC10 angular inactivates both Akt and ERK, which results in Foxo3a nuclear factor migration to the nucleus and binding to TRAIL promoter.
SML1862 TP-472 ≥98% (HPLC) TP-472 is a selective probe for bromodomain-containing proteins BRD9 and BRD7. This BRD9/7 probe was developed out of a collaborative effort by Takeda and the SGC, and is of a different chemotype from BRD9/7 probes previously available. TP-472 has a KD value of 33nM for BRD9 and 340nM for BRD7 by ITC. It is >30 fold selective for BRD9 over all other bromodomain family members except BRD7. It is suitable for in vivo applications. For full characterization details, please visit the TP-472 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
T5202 TPBM ≥98% (HPLC), solid TPBM is a potent inhibitor of estrogen receptor α via blocking ERα binding to consensus estrogen response element (cERE) DNA. Estrogen receptor α (ERα) plays an important role in several human cancers. Current ERα antagonists bind in the receptor ligand binding pocket and compete for binding with estrogenic ligands. TPBM instead inhibits ERα via binding to consensus estrogen response element (cERE) DNA. TPBM is not toxic to cells and does not effect estrogen-independent cell growth. TPBM does not act by chelating the zinc in ERs zinc fingers and differs from known ERα inhibitors.
SML0232 TPSF ≥98% (HPLC) TPSF is a noncompetitive, potent inhibitor of estrogen receptor α, that does not compete with estrogen for binding to Erα. The compound has low toxicity and selectively targets E2-ERα-dependent cell growth. TPSF is effective in cells that become tamoxifen-resistant. It appears that down-regulation of ERα by TPSF is at list partially dependent to enhancement of proteasome-dependent degradation of ERα.
T4080 6, 2′, 4′-trimethoxyflavone ≥98% (HPLC) 6, 2′, 4′-trimethoxyflavone is a selective aryl hydrocarbon receptor (AHR) antagonist with no partial agonist activity. The role of the transcription factor aryl hydrocarbon receptor (AHR) in biology is still under evaluation and has expanded beyond that of a xenobiotic sensor and regulator of detoxification. Inhibition of AHR activity by antagonists could result in anti-inflammatory actions. 6, 2′, 4′-trimethoxyflavone (TMF) is a pure AHR antagonist. The compound compete with agonists, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (B[a]P), thus effectively inhibiting AHRmediated transactivation of a heterologous reporter and endogenous targets e.g. CYP1A1. TMF also exhibits no species or promoter dependency with regard to AHR antagonism. Thus it represents an improved tool allowing for more precise dissection of AHR function.
SML0662 UNC1215 ≥98% (HPLC) UNC1215 is a potent, selective antagonist of L3MBTL3 with cellular activity. Lethal (3) malignant brain tumor-like protein 3 (L3MBTL3) is a putative polycomb group (PcG) protein with gene-repressing activity, a member of the MBT family of methyllysine binders. Methyl-lysine binding proteins are a family of proteins that are important epigenetic regulators that “read” the post-translational methylation state of histone lysine residues and modulate protein-protein interactions that regulate gene expression. UNC1215 has an IC50 of 20 nM and > 100-fold selectivity over 13 HMTs and selected representatives of kinases, ion channels, 7TMs, and other epigenetic proteins. UNC1215 showed a significant decrease in FRAP recovery (Fluorescence Recovery After Photobleaching) time below 1 microM in cells using GFP-L3MBTL3. For full characterization details, please visit the UNC1215 probe summary on the Structural Genomics Consortium (SGC) website.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
SML1434 UNC2170 trifluoroacetate ≥98% (HPLC) UNC2170 is an inhibitor of DNA damage response protein 53BP1, which recognizes dimthyl lysine residues on lysine 20 on histone H4 that is involved in double-strand DNA breaks. 17-fold selectivity for 53BP1 as compared to other methyl-lysine (Kme) binding proteins tested.
SML0554 UNC926 ≥98% (HPLC) UNC926 is a specific antagonist of the methyl-lysine binding protein L3MBTL1, a member of a protein family that reads the methylation state of histone lysine residues to direct gene expression. UNC926 dose dependently blocks the interaction of recombinant L3MBTL carrying three tandem MBT reader domains (L3MBTL3XMBT) and a methylated histone peptide H4K20me1 with an IC50 of 3.9 μM.
SML1896 VH298 ≥98% (HPLC) New VH298 is a cell-permeable small molecule that disrupts the interaction of VHL with Hypoxia-inducible factor HIF-α, stabilizing HIF-α and inducing a hypoxic response. Hypoxia-inducible factors (HIFs) are oxygen-sensitive transcription factors that regulate hypoxic signalling. They are regulated by oxygen-dependent prolyl hydroxylase domain (PHD) enzymes and polyubiquitination by the von Hippel–Lindau (VHL) Cullin RING E3 ubiquitin ligase complex. Unlike many PHD inhibitors, which have off-target effects, VH298 acts downstream of the PHD enzymes, inhibiting the VHL:HIF-α interaction. VH298 had a Kd of 90 nM. VH298 was shown to induce HIF transcriptional activity, to increase accumulation of HIF-α in HeLa cells and to stimulate erythropoietin production in RCC4 cells.
SML1230 XW4.4 ≥98% (HPLC) XW4.4 can generate insulin-producing cells from rat mesenchymal stem cells. XW4.4 induced pancreatic differentiation of rat bone marrow derived mesenchymal stem cells into insulin-producing cells shown to release C-peptide and insulin in response to physiological or high glucose levels, which could lead to a possible treatment for Type 1 diabetes. Its mechanism of action is postulated to be through increasing expression of hepatocyte nuclear factor 3β (HNF3β), a member of the forkhead box transcription factor family that regulates expression of several genes in the pancreas during early embryogenesis.
Y1646 YH439 ≥98% (HPLC) YH439 is an aryl hydrocarbon receptor activator