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PPAR and RXR Regulators

PPAR Signaling Pathway
Similar to other nuclear hormone receptors, peroxisome proliferator-activated receptors (PPARs) act as ligand-activated transcription factors. When bound to its fatty acid ligand, PPARα forms a heterodimeric complex with the retinoid X receptor (RXR) to regulate transcription. PPARγ is activated by prostaglandins and leukotrienes and regulates the gene expression of proteins involved in the storage of fatty acids. PPARβ is weakly activated by fatty acids, prostaglandins, and leukotrienes. Its physiological ligand has not been identified.
References:
Fajas, L., et al., Peroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis. J. Mol. Endocrinol., 27, 1-9 (2001).
Qi, C., et al., Peroxisome proliferator-activated receptors, coactivators, and downstream targets. Cell. Biochem. Biophys., 32, 187-204 (2000).

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SML0510 S 26948 ≥98% (HPLC) S 26948 is a selective PPARγ modulator (SPPARγM). S 26948 is as effective as rosiglitazone in reducing insulin resistance and lipid homeostasis, but does not increase body or white adipose tissue weight. S 26948 also leads to different co-activatior recruitment to PPARγ than rosiglitazone.
230950 Ciglitazone - CAS 74772-77-3 - Calbiochem A potent thiazolinedione (TDZ) type anti-hyperglycemic agent and a selective PPARγ agonist (EC₅₀ = 3 µM).  
370695 GW1929 - CAS 196808-24-9 - Calbiochem A potent, tyrosine-based peroxisome proliferator-activated receptor γ (PPARγ) agonist (EC₅₀ = 13 nM for murine receptor and 6.2 nM for human receptor in cell-based transactivation assays).  
370698 GW7647 - CAS 265129-71-3 - Calbiochem A cell-permeable urea-substituted thioisobutyric acid compound that acts as a potent and selective PPARα.  
422175 L-165,041 - CAS 79558-09-1 - Calbiochem A cell-permeable phenoxyacetic acid derivative that acts as a potent and selective peroxisome proliferator activator receptor δ (PPARδ) agonist (Ki = 6 nM for hPPARδ and 730 nM for hPPARγ).  
516566 PPARγ Antagonist III, G3335 - CAS 36099-95-3 - Calbiochem The PPARγ Antagonist III, G3335, also referenced under CAS 36099-95-3, controls the biological activity of PPARγ.  
516567 PPARβ/δ Antagonist, GSK3787 - CAS 188591-46-0 - Calbiochem The PPARβ/δAntagonist II, PT-S58, also referenced under CAS 188591-46-0, controls the biological activity of PPARβ/δ. This small molecule/inhibitor is primarily used for Biochemicals applications.  
516568 PPARβ/δ Inverse Agonist - Calbiochem The PPARβ/δ Inverse Agonist controls the biological activity of PPARβ/δ.  
516569 PPARβ/δ Antagonist, PT-S58 - Calbiochem The PPARβ/δ Antagonist, PT-S58 controls the biological activity of PPARβ/δ.  
516570-M PPARγ Modulator, SR1664 - Calbiochem A cell-permeable non-thiazolidinediones derivative that binds tightly to peroxisome proliferator-activated γ (PPAR-γ) receptor, but does not exhibit any transcriptional agonism.  
516571 PPAR Agonist IX, GQ-16 - Calbiochem The PPAR Agonist IX, GQ-16 controls the biological activity of PPAR. This small molecule/inhibitor is primarily used for Biochemicals applications.  
557366-M Rosiglitazone - CAS 155141-29-0 - Calbiochem A thiazolidinedione compound that acts as an anti-diabetic agent and serves as a potent and selective agonist of peroxisome proliferator-activated receptor-γ (PPARγ) (Kd ~40 nM) in fat cells.  
648469-M Troglitazone - CAS 97322-87-7 - Calbiochem A α-tocopherol (vitamin E) moiety containing thiazolidinedione class of insulin-sensitizer that acts as an activator of peroxisome proliferator-activated receptors γ (PPARγ).  
681725-M WY-14643 - CAS 50892-23-4 - Calbiochem One of the most potent peroxisome proliferator-activated receptor α (PPARα) ligands.  
A3111 A1120 ≥98% (HPLC), powder A1120 is a selective non-retinoid ligand for retinol-binding protein 4 (RBP4). RBP4 transports retinol from the liver to extrahepatic tissues and RBP4 lowering is reported to improve insulin sensitivity in mice. A1120 is a high affinity non-retinoid ligand for RBP4 which disrupts the interaction between RBP4 and its binding partner transthyretin (TTR). It binds to the same site as retinol and induces changes in the orientation (compared to the retinol bound form) of loops at the RBP4-TTR interaction interface.A1120 lowers RBP4 and retinol levels in a dose-dependent manner, to a similar extent as seen with fenretinide. However, unlike fenretinide (Sigma# H7779), A1120 does not have beneficial effects on insulin resistance.
A7980 AC-41848 hydrate ≥98% (HPLC), solid AC-41848 is a potent, cell permeable, subtype selective retinoic acid receptor RARγ agonist. AC-41848 has high selectivity (92%) for RARγ. EC50 = 5.9 μM.
A9480 AC-55649 ≥98% (HPLC), solid AC-55649 is a subtype selective RAR (RARβ2) agonist. AC-55649 is a potent, orally available isoform selective Retinoic Acid Receptor β2. AC-55649 has high selectivity, 99% for RARβ2 and 31% for RARβ1. When compared to the gold standard AM-580 (Cat. No A8843), both isoform receptors were 100%. AC-55649 has a potent EC50 of 6.9 μM compared to an EC50 of 7.7 μM for AM-580.
A9605 AC-93253 iodide ≥98% (HPLC) AC-93253 is a potent, cell permeable, subtype selective RAR (RARα) agonist. EC50 = 6.3 μM. AC-93253 has high selectivity; 89% for RARα vs 67% for RARβ1, 35% for RARβ2, and 11% for RARγ.
A7486 Adapalene ≥98% (HPLC) Retinoic acid analogue that is a RARβ and RARγ agonist (AC50 values are 2.2, 9.3, 22 and > 1000 nM for RARβ, RARγ, RARα and RXRα receptors respectively). Inhibits proliferation and induces apoptosis in colorectal cancer cells in vitro. Displays comedolytic activity. Its unique pharmacological properties make it superior to other retinoids for the treatment of acne.
A8843 AM580 ≥98% (HPLC)  
SML0921 AR7 ≥98% (HPLC) AR7 is an atypical retinoic acid receptor α (RARα) antagonist. There is high interest in retinoic acid receptors for cancer and for differentiation studies. Recently, it has been found that signaling through retinoic acid receptor α (RARα) inhibits chaperone-mediated autophagy (CMA). Disruption of RARα signaling has a stimulatory effect on CMA, but can lead to inhibition of macroautophagy. AR7 antagonizes only the CMA inhibitory effect without affecting macroautophagy, allowing the two RARα effects on autophagy to be studied independently.
A6850 Azelaoyl PAF 10 mg/mL in ethanol Potent PPARγ agonist.
SML0282 Bexarotene ≥98% (HPLC) Bexarotene is a highly selective retinoid X receptor (RXR) agonist. It is an antineoplastic agent, already approved as an oral antineoplastic agent for cutaneous T cell lymphoma and being investigated against other cancers. A study has found that bexarotene in a mouse Alzheimer′s model lowered the most toxic form of β-amyloid peptide and increased cognitive ability. The activity in the mouse Alzheimer′s models are believed to be by activating PPARγ:RXR and LXR:RXR dimers which induces the expression of apoE and facilitates Aβ clearance and promotes microglial phagocytosis.
B7273 Bezafibrate ≥98%, solid The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid nuclear receptor superfamily. Bezafibrate is a peroxisome proliferator-activated receptor agonist for PPARα, PPARδ, and PPARγ. Lipoprotein lipase (LPL) activator.
PPARgamma agonists, including Bezafibrate, have beneficial effects in the suppression of the inflammatory response during RSV infection and therefore might have clinical efficacy in the course of severe RSV-infection.
D3415 Bisphenol A diglycidyl ether PPARγ inhibitor that blocks rosiglitazone- and insulin-induced adipogenesis.
SML1149 BMS-189453 ≥98% (HPLC) BMS-189453 is a potent RARβ agonist that acts as an antagonist against RARα and RARγ. BMS-189453 induces RARβ reporter gene expression at sub nanomolar levels, and is 30 fold more potent than all-trans retinoic acid for inducing TGFβ activity in normal breast cells. The compound BMS-189453 does not transactivate RARα or γ transcriptional activity, but binding to those family members induces a strong transrepression of phorbol ester-induced AP-1 activity (IC50 = 0.1 nM in HeLa and MCSF-7). BMS-189453 significantly increases the efficiency of cardiac differentiation of hESCs.
SML1084 BMS-195614 ≥97% (HPLC) BMS-195614 (BMS614) is a potent neutral retinoic acid receptor RARα selective antagonist with an IC50 of 2.5 nM.
B6688 BMS 493 ≥98% (HPLC) BMS 493 is an inverse pan-RAR agonist. Retinoic acid receptors (RARs) are ligand-dependent transcription factors that control a number of physiological processes. RARs exert their functions by regulating gene networks controlling cell growth, differentiation, survival, and death.
SML0286 BMS 753 ≥98% (HPLC) BMS 753 is a very potent, specific agonist for RARa (Ki = 2 nM). BMS 753 does not display significant effects on RARg in reporter based assays, or in binding assays measuring displacement of labeled retinoic acid.
238422 2-Bromohexadecanoic acid ~97% 2-Bromohexadecanoic acid is a PPARδ agonist. It has also been shown to inhibit fatty acid oxidation, inhibit DHHC-mediated palmitoylation, and promote glucose uptake in rat cardiac cells and the insulin-sensitive murine fibroblast line A31-IS.
B4438 BVT.13 hydrate ≥98% (HPLC) BVT.13 is a potent and selective PPAR-γ activator.
SML1759 CD1530 ≥98% (HPLC) CD1530 is a potent and selective agonist of retinoic acid receptor RARγ with Kd values of 150, 1,500, and 2,750 nM for RARγ, RARβ, and RARα receptors, respectively. In various studies, CD1530 has been shown to preserve human tendon stem cell characteristics, promote repair of injured skeletal muscle, and in combination with bexarotene to inhibit oral carcinogenesis.
C5865 CD437 ≥98% (HPLC), solid CD437 is a retinoic acid receptor (RAR)γ-selective agonist, γ-selective retinoid; potent inducer of apoptosis.
C5749 CGP 52608 ≥98%, solid CGP 52608 is a specific activator of retinoic acid receptor-related orphan receptor α (RORA).
C3974 Ciglitizone ≥98% (HPLC) Selective peroxisome proliferator-activated receptor-γ (PPARγ) agonist (EC50 = 3 μM) and antihyperglycemic agent displaying activity in genetically obese C57 B1/6 ob/ob mice.
C0330 Ciprofibrate Peroxisome proliferator-activated receptor α (PPARα) agonist
PZ0173 CP-775146 ≥98% (HPLC) CP-775146 is a potent and selective PPARα agonist.
PZ0149 CP-868388 ≥98% (HPLC) CP-868388 is a potent PPARα agonist with a Ki of 10.8 nM.
SML0977 Darglitazone sodium salt ≥98% (HPLC) Darglitazone is a highly potent and selective PPAR-γ (peroxisome proliferator-activated receptor-γ) agonist. Darglitazone is a thiazolidinedione approximately 200x more potent than ciglitazone. Darglitazone restores euglycemia and reduced circulating TG and VLDL in the ob/ob mice. Also Darglitazone offers a significant neuroprotection and promotes recovery after a hypoxic-ischemic insult in the diabetic ob/ob mouse.
SML1835 DSHN ≥98% (HPLC) New DSHN is a potent and selective activator of SHP (small heterodimer partner, NR0B2) that transcriptionally activates SHP mRNA and stabilized the SHP protein by preventing its ubiquitination and degradation. DSHN potently inhibits HCC cell migration and invasivnes by suppression of CCL2 expression.
F5682 FH535 ≥98% (HPLC) FH535 is a reversible dual inhibitor of Wnt/β-catenin and a PPARγ and PPARδ signaling antagonist. FH535 is unique in its ability to inhibit the Wnt/β-catenin pathway. The compound is selectively toxic to some carcinomas expressing the Wnt/β-catenin pathway.
SML1449 G3335 ≥98% (HPLC) G3335 ( L-tryptophyl-L-glutamic acid) is a cell-permeable dipeptide that acts as a selective and reversible PPARγ antagonist with a Kd value of 8.34 μM for PPARγ and much lower activity at other PPAR subtypes. G3335 reversibly and competitively blocks activation of PPARγ by the PPARγ agonist rosiglitazone, and conversely, in rat astrocyte culture higher levels of rosiglitazone reduced harmful effects induced by G3335. At higher concentration G3335 may act as a PPARα agonist, interacting with the PPARα ligand binding domain with a KD of 120 μM. G3335 is reported to reduce hepatic lipid accumulation in lipid-loaded hepatocytes by activation of PPARα.
G5797 GSK0660 ≥98% (HPLC) GSK0660 is a potent PPARβ/δ antagonist with a pIC50 of 6.8 (160 nM). GSK0660 is nearly inactive on PPARα and PPARγ with IC50s greater than 10 μM.
SML1617 GSK2033 ≥98% (HPLC) GSK2033 is an antagonist of the nuclear receptor liver-X-receptor (LXR) with pIC50 values of 7.0 for LXRα and 7.4 for LXRβ. Treatment of murine CD41 T cells with GSK2033 enhanced cellular proliferation and Th1/Th2/Th17 differentiation. In another study, the conjugated linoleic acid (CLA)-induced expression of efflux protein ATP-binding-cassette transporter A1 (ABCA1) was completely abolished by preincubation with GSK2033, showing that CLA mediated regulation of ABCA-1 expression is LXR dependent.
G3295 GW0742 ≥98% (HPLC) GW0742 is a highly selective PPARδ agonist. EC50 = 1 nM vs 1 μM and 2 μM for PPARα and PPARγ, respectively.
G5668 GW1929 hydrate >98% (HPLC), solid GW1929 is a high affinity agonist of PPAR-γ.
G6295 GW3965 hydrochloride ≥98% (HPLC), powder GW3965 is a liver X receptor full agonist on hLXRα and hLXRβ. GW3965 has an EC50 = 125 nM in a cell-free ligand-sensing assay of LXRα and profiles as a full agonist on hLXRα and hLXRβ in cell-based assays with EC50 = 190 nM and 30 nM, respectively. It is orally active in mice. When screened against a panel of nuclear receptors, it cross-reacted with only the pregnane X receptor (PXR). The literature agonist, T0901317 (Tularik), had an EC50 = 60 nM and 85 nM in the cell-free and cell-based assays, respectively.
SML1491 GW501516 ≥98% (HPLC) GW501516 is a selective Peroxisome Proliferator-Activated Receptor delta (PPARδ) agonist with high affinity (Ki = 1 nM) and potency (EC50 = 1 nM) for PPARδ and > 1000 fold selectivity over PPARα and PPARγ. GW501516 was shown to activate some of the same pathways activated through exercise, and was investigated as a potential treatment for obesity, diabetes, dyslipidemia and cardiovascular disease. However, GW501516 also showed an increase in cancer in rats.
G5045 GW6471 ≥98% (HPLC) GW6471 is a PPARα antagonist, which completely inhibits GW409544-induced activation of PPARα with an IC50 = 0.24 μM. GW6471 induces a PPARα conformation that interacts efficiently with co-repressors.
G6793 GW7647 ≥98% (HPLC) Potent human PPARα agonist. Use to study the biology of PPARα receptor in human cells.
M6191 GW9662 >98% (HPLC) GW9662 is an irreversible PPARγ antagonist. GW9662 inhibits connective tissue growth factor and activation of CD36 by IL-4.
H9146 13(S)-Hydroxyoctadeca-9Z,11E-dienoic acid 90-100 μg/mL in ethanol, ≥98% Expression of 15-lipoxygenase-1 (15-LOX-1) and its main product, 13(S)-HODE, are decreased in human colorectal and esophageal cancers. Certain non-steroidal anti-inflammatory drugs (NSAIDs) can induce apoptosis in human colon cancer cells by increased expression of 15-LOX-1, which down-regulates PPAR-delta through 13-HODE.
PPARγ agonist
L2167 L-165,041 ≥98% (HPLC), powder PPARβ (PPARδ) selective agonist.
SML0809 LE 135 ≥98% (HPLC) LE135 is a retinoic acid receptor (RAR) antagonist with selectivity for RARβ (Ki = 220 nM) over RARα (Ki = 1.4 μM). LE135 inhibits retinoic acid-induced transcriptional activation of RARβ (>70% inhibition at 10 μM), but not RARα, RARγ or retinoid X receptor α (RXRα). There is high interest in retinoic acid receptors for cancer and for differentiation studies. LE135 has been shown to inhibit retinoid Am80-induced differentiation of human promyelocytic leukemia HL-60 cells with an IC50 value of 0.2 μM. LE135 has been used to study the role of a retinoic acid receptor-β (RARβ) on the differentiation of mesenchymal stem cells, and was found to inhibit the neuronal differentiation promoting effects of all-trans retinoic acid (ATRA) on mesenchymal stem cells.
SML0279 LG100268 ≥98% (HPLC) LG100268 (LG268) is a potent and selective rexinoid and retinoid-X receptor (RXR) agonist. LG100268 binds to the α, β and γ RXR receptors with an IC50 = 3-4 nM and has no activity at the RAR retinoic acid receptors.
SML0771 LG100754 ≥98% (HPLC) LG100754 is a unique RXR ligand that acts as an antagonist against RXR homodimers, but is a strong agonist for RXR:PPARα and RXR:PPARγ heterodimers. The compound does not have agonist activities for other RXR heterodimers containing LXR or GAR/FXR receptors. LG100754 initiates adipocyte differentiation, inhibits TNFα-induced insulin receptor hypophosphorylation and improves insulin resistance in db/db mice.
SML0600 LPSF/GQ-02 ≥98% (HPLC) LPSF/GQ-02 is a new thiazolidinedione that shows improved insulin resistance, reduces the area of atherosclerotic lesions, and offers a protective effect for the endothelium in LDL receptor-deficient mice. LPSF/GQ-02 induced an overexpression of eNOS and significantly inhibited the expression of metalloproteinases, both of which can result in anti-inflammatory effects.
SML1201 LT175 ≥98% (HPLC) LT175 is a dual PPARα/γ agonist that exhibit partial agonist profile at PPARγ. LT175 modulates lipid and glucose metabolism with reduced adipogenic activity. Also, LT175 significantly reduces plasma glucose, insulin, non-esterified fatty acids, triglycerides and cholesterol. LT175 decreases body weight, adipocyte size and white adipose tissue mass in mice on high fat diet. It appears that LT175 binds to different region of PPARγ than rosiglitazone (and other glitazones).
SML0064 MBX-102 ≥98% (HPLC) MBX-102 has a potent transrepression effect on PPARγ. It is an oral glucose-reducing agent and also has insulin-sensitizing properties. It is useful as treatment for type 2 diabetes. MBX-102 also lowers triglycerides in a PPARα-independent manner.
MBX-102 is a selective PPAR modulator (SPPARM) and has been shown to inhibit phosphorylation of PPARγ. MBX-102 is converted to the active form, MBX-102 acid, in vivo.
M5824 MBX-102 acid ≥98% (HPLC), powder MBX-102 is a selective PPAR modulator (SPPARM) and has been shown to inhibit phosphorylation of PPARγ.
SML0896 MCC-555 ≥98% (HPLC) MCC-555 is a thiazolidinedione class anti-diabetic compound. In rodent models, MCC-555 attenuates the development of diabetes, maintains B-cell function and improves insulin sensitivity. The compound MCC-555 also inhibits proliferation of several cancer cell lines and reduces tumor growth in xenograft models.
SML0616 nTZDpa ≥98% (HPLC) nTZDpa is a non-thiazolidinedione PPARγ partial agonist and selective PPARγ modulator (SPPARγM). nTZDpa binds to PPARγ with high affinity, but partially activates the receptor in cell-based assays. nTZDpa reduces insulin resistance and hyperglycemia in obese diabetic rodents equal to TZD full agonists, but without increasing cardiac weight and adiposity.
O1639 N-(3-Oxooctanoyl)-DL-homoserine lactone ≥97% (HPLC), white powder N-(3-Oxooctanoyl)-DL-homoserine lactone stimulates the tra gene expression. It is an autoinducer and potent antagonist.
O1764 N-(3-Oxooctanoyl)-L-homoserine lactone ≥97% (HPLC), white powder N-(3-Oxooctanoyl)-L-homoserine lactone stimulates the tra gene expression. It is an autoinducer and potent antagonist.
SRP0425 PARP10 active human recombinant, expressed in baculovirus infected Sf9 cells, ≥68% (SDS-PAGE)  
SRP0422 PARP5A active human recombinant, expressed in baculovirus infected Sf9 cells, ≥30% (SDS-PAGE)  
E6910 Pioglitazone hydrochloride ≥98% (HPLC) Pioglitazone hydrochloride is a PPARγ agonist and thiazolidinedione (TZD) anti-diabetic. Pioglitazone is a selective agonist of the nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ) and to a lesser extent PPAR-α.
SML0410 PT-S58 ≥98% (HPLC) PT-S58 is a PPAR β/δ full antagonist, and a derivative of GSK0660. PT-S58 has a three-fold higher affinity for the receptor than GSK0660 and is a potent inhibitor of agonist-induced target gene expression. Unlike GSK0660, PT-S58 blocks the recruitment co-repressor molecules such as SMRT.
R2625 Retinoic acid ≥98% (HPLC), powder all−trans−Retinoic acid (ATRA) is a ligand for both the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). The bound RAR and RXR act as transcription factors that regulate the growth and differentiation of both normal and malignant cells. Cytochromes P450 (CYPs) catalyze the 4-hydroxylation of ATRA. Retinoic acid primes embryonic stem cells to become neurons.
R4643 9-cis-Retinoic acid ≥98% (HPLC) Ligand for both the retinoic acid receptor (RAR) and the retinoid X receptor (RXR) that act as transcription factors to regulate the growth and differentiation of normal and malignant cells.
R3255 13-cis-Retinoic acid ≥98% (HPLC) 13-cis-Retinoic acid (RA) has anti-inflammatory and anti-tumor action. The action of RA is mediated through RAR-β and RAR-α receptors. RA attenuates iNOS expression and activity in cytokine-stimulated murine mesangial cells. It induces mitochondrial membrane permeability transition, observed as swelling and as a decrease in membrane potential, and stimulates the release of cytochrome c implicating mechanisms through the apoptosis pathway. These activities are reversed by EGTA and cyclosporin A. RA also increases MMP-1 protein expression partially via increased transcription.
H7779 Retinoic acid p-hydroxyanilide ≥95% Vitamin A acid analogue with antiproliferative activity in cultured human breast cancer cells; induces apoptosis in malignant hemopoietic cell lines.
SML0573 Ro 41-5253 ≥98% (HPLC) Ro 41-5253 ( GR110) is a potent (IC50 = 16 nM) and selective retinoic acid receptor-α (RARα) antagonist, with some recently discovered activity as a PPARγ agonist at 50-fold higher concentrations (EC50 = 810 nM). Ro 41-5253 inhibited differentiation and prevented the loss of human HSCs that otherwise occurs in short-term culture.
SML0738 RORγ Activator 1b ≥98% (HPLC) RORγ Activator 1b binds to the retinoid-related orphan receptor RORγ and induces IL-17 reporter gene expression with an EC50 of 0.1 μM. The compound RORγ Activator 1b enhances differentiation of CD4+ T cells to IL-17-secreting cells with a maximum effect of 220 percent of control at 3 μM.
R2408 Rosiglitazone ≥98% (HPLC) Rosiglitazone is a potent agonist for PPARγ with an EC50 of 43 nM for the human receptor. It is antidiabetic, working as an insulin sensitizer by binding to the PPARγ receptors in fat cells and making the cells more responsive to insulin.
SML1778 SR0987 ≥98% (HPLC) SR0987 is a cell-permeable SR1078 analog with ~6-fold improved agonist potency toward T-cell-specific retinoic acid receptor-related orphan receptor ROR?t (EC50 ~800 nM in cell-based reporter assays) by targeting an allosteric pocket within the RORγt ligand-binding domain (LBD). In addition to upregulating RORγt target gene IL17A expression, SR0987 is shown to simultaneously downregulate surface immune checkpoint protein PD-1 expression by a yet unidentified mechanism among ex vivo differentiated murine TH17 cells, as well as PMA/ionophore-stimulated human Jurkat T cells and murine EL4 T lymphocytes.
SML0322 SR1001 ≥98% (HPLC) SR1001 is an antagonist of the nuclear retinoic acid receptor-related orphan receptors RORα and RORγt with no activity at LXR or RORβ. RORα and RORγt are essential for the development of TH17 cells, T-helper cells that produce interleukin-17 and have recently been shown to have pathological roles in various autoimmune diseases. SR1001 binds to the ligand-binding domain of RORα and RORγt to decrease affinity of the receptor for coactivators and increse affinity for co-repressors. It inhibited the differentiation and function of TH17 cells and suppressed the clinical severity of a mouse model of multiple sclerosis.
S8951 SR11237 ≥98% (HPLC) SR11237 and other ligands of retinoid X receptor (RXR) activate various nuclear receptors during development process. This produces malformations in Xenopus embryos, involving the anterior-posterior axis.1
SR11237 is a selective pan retinoid X receptor (RXR) agonist with no retinoid A receptor (RAR) activity.
SML0765 SR1555 ≥98% (HPLC) SR1555 is a selective RORγ inverse agonist that inhibits the development and function of TH17 cells, a subset of T cells that have been implicated in the pathology of several autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. SR1555 also increases the frequency of T regulatory cells, an effect not seen with previously described RORγ ligands.
SML0636 SR1664 ≥98% (HPLC) SR1664 is a non-agonist PPARγ ligand and an inhibitor of Cdk5-mediated PPARγ phosphorylation. It has strong antidiabetic activity in two murine models of diabetes without the side effects normally asociated with the thiazolidinedione (TZD) antidiabetic PPARγ agonists. The TZD antidiabetics such as rosiglitazone and pioglitazone are full PPARγ agonists, but recent data have suggested that their separate activity, inhibition of the the obesity-linked PPARγ phosphorylation by Cdk5, is likely the more important activity for antidiabetic action. SR1664 has an IC50 of 80 nM in a competitive binding assay, blocked the Cdk5-mediated phosphorylation of PPARγ in vitro with IC50 between 20 and 200 nM and exhibited no PPARγ agonist activity.
S1320 SR-202 ≥98% (HPLC), crystalline SR-202 is a selective PPARγ antagonist. Improves insulin sensitivity in diabetic mice.
SML1170 SR2211 ≥98% (HPLC) SR2211 (ML310) is a potent and selective inverse agonist of retinoic acid receptor-related orphan receptor gamma (RORγ). RORγ is essential for interleukin 17 expression and differentiation of TH17 cells, important in autoimmune diseases including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and lupus. SR2211 (ML310) treatment of EL-4 murine T lymphocyte cells resulted in suppression of gene expression and production of IL-17 with an IC50 ~320 nM with no effect on the transcriptional activity of RORγ. In a mouse model of rheumatoid arthritis, SR2211 significantly reduced joint inflammation, suppressing inflammatory T cell function, expression and production of inflammatory cytokines, and macrophage activation.
SML1510 SR9238 ≥98% (HPLC) SR9238 is liver selective LXR inverse agonist with high potency for both LXRα and LXRβ with an IC50 of 214 nM for LXRα and 43 nM for LXRβ. Metabolic syndrome is often accompanied by liver problems, such as fatty liver (nonalcoholic hepatosteatosis), associated with increased lipogenesis. Liver X receptors α and β (LXRα and LXRβ) are known to induce lipogenesis by increasing transcription of lipogenic enzyme genes, so it was hoped LXR antagonists might be of use in fatty liver. In a mouse model of nonalcoholic hepatosteatosis, SR9238 reduced the expression of lipogenic genes, and suppressed hepatic lipogenesis, inflammation and hepatic lipid accumulation. It was also effective in reduction of hepatic fibrosis in another study. Additionally in diet induced obese mice, SR9238 suppressed plasma cholesterol levels.
SML1517 SR9243 ≥98% (HPLC) SR9243 is a selective inverse agonist of the nuclear receptor liver-X-receptor (LXR) that targets the Warburg effect, inhibiting glycolysis and lipogenesis by reducing glycolytic and lipogenic gene expression. SR9243 is believed to enhance corepressor recruitment to LXRs at target-gene promoters, resulting in suppression of gene expression. SR9243 induced apoptosis in tumor cells without harming normal cells. SR9243 reduced prostate, colorectal, and lung cancer cell viability at nanomolar concentrations and also inhibited colon tumor xenograft growth.
SML0424 ST247 ≥98% (HPLC) ST247 is a PPAR β/δ selective inverse agonist. The compound is based on the structure of GSK0660, and is 10-fold more potent in blocking the transcription of endogenous target genes: ST247 IC50 = 19 nm vs. GSK0660 IC50 = 210 nM.
T8703 T0070907 ≥98% (HPLC) T0070907 is very similar in structure and activity to the PPAR-γ antagonist GW9662. T0070907 is more potent and has higher selectivity for PPAR-γ over all other subtypes (about 800-fold) whereas GW9662 has been reported to have some PPAR-α agonist activity.
T2320 T0901317 ≥98% LXR agonist whose treatment results in an LXR-dependent up-regulation of ABC1 gene expression
T3205 Tamibarotene ≥98% (HPLC) Tamibarotene (Am80) is a RAR α agonist. Tamibarotene was developed to overcome resistance to ATRA and is currently approved in Japan for treatment of recurrent acute promyelocytic leukemia (APL). The compound induces HL-60 cells differentiation and apoptosis. Similarly to TTNPB, the compound neither binds to nor transactivates the RXRs. In contrast to TTNPB (pan RAR agonist), Tamibarotene is rather specific toward RAR α. The compound is approximate 10 times more potent than ATRA.
T7080 Tazarotene ≥98% (HPLC) Tazarotene induces the expression of tazarotene-induced gene 3 (TIG3), a tumor suppressor gene. It is a prodrug of tazarotenic acid, which specifically activates RARb and RARg, only weakly activates RARa, and is inactive at retinoid X receptors (RXRs). In psoriasis, tazarotene normalizes abnormal keratinocyte differentiation and reduces their hyperproliferation.
SML1619 Tazarotenic acid ≥98% (HPLC) Tazarotenic acid, an active metabolite of tazarotene, is a potent and selective agonist of the retinoid receptor (RAR) that binds to RARα, RARβ, and RARγ. Tazarotenic acid relatively selective activates RARβ and RARγ. Tazarotenic acid is a first xenobiotic substrate of human retinoic acid hydroxylase CYP26A1 and CYP26B1.
SML1369 Tesaglitazar ≥98% (HPLC) Tesaglitazar is a potent and specific dual PPARα/γ agonist that improves insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats.
T1698 Tetradecylthioacetic acid ≥97% (NMR) PPARα agonist; activation in ranking order: PPARδ > PPARα > PPARγ
Tetradecylthioacetic acid (TTA) is known to modulate lipid homeostasis. TTA can increase fatty acid oxidation and ketogenesis, which can subsequently prevent adiposity and insulin resistance. Furthermore, TTA can enhance cardiac functions during experimental heart failure.
T2573 Troglitazone ≥98% (HPLC) PPARγ agonist; anti-diabetic thiazolidinedione (TZD) with anti-inflammatory and anti-tumor activity; induces apoptosis via a p53 pathway.
SML1280 TT01001 ≥98% (HPLC) TT01001 is potent, orally available the mitochondrial outer membrane protein mitoNEET ligands that binds to mitoNEET without PPARγ activation. TT01001 improves hyperglycemia, hyperlipidemia, and glucose intolerance in mice models of diabetes II. TT01001 exerts anti-diabetic effects without the pioglitazone associated weight gain.
T3757 TTNPB Selective and highly potent retinoic acid analog with affinity for retinoic acid receptors (RAR) α, β, and γ, which are nuclear transcription factors. Produces ligand-activated transcription of genes that possess retinoic acid responsive elements.
C7081 WY-14643 Selective PPARα agonist.
X4753 XCT790 ≥98% (HPLC), solid XCT790 is a potent and specific inverse agonist of ERRα. XCT790 is selective; showing no significant antagonist activity on related nuclear receptors, such as ERRγ or ERα at concentrations below 10 μM. XCT790 inhibits the constitutive activity of ERRα in both biochemical and cell-based assays. The IC50 value is 300-500 nM in transient transfection assays using GAL4-ERR LBD or full-length ERR with the mSHP promoter.
SML0802 ZLN005 ≥95% (HPLC) ZLN005 is a transcriptional regulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). ZLN005 increased PGC-1 and downstream gene transcription in skeletal muscle, while reducing hepatic PGC-1α and gluconeogenesis genes. ZLN005 increased fat oxidation and improved the glucose tolerance, pyruvate tolerance, insulin sensitivity, hyperglycemia and dyslipidemia of diabetic db/db mice.