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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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% (TLC)  
    • 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.
    • 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 palmitoylation1, and promote glucose uptake in rat cardiac cells and the insulin-sensitive murine fibroblast line A31-IS2.
    • B4438 BVT.13 hydrate ≥98% (HPLC) BVT.13 is a potent and selective PPAR-γ activator.
    • 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 ≥99% (TLC) 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.
    • 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.
    • 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.
    • G3295 GW0742 ≥98% (HPLC), solid GW0742 is a highly selective PPARδ agonist. EC50 = 1 nM vs 1 and 2 mM 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.
    • G5045 GW6471 solid, ≥98% (HPLC), off-white to light yellow 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.
    • 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.
    • SML0600 LPSF/GQ-02 ≥98% (HPLC) New 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.
    • SML0064 MBX-102 ≥98% (HPLC) 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.
    • SML0616 nTZDpa ≥98% (HPLC) New 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) New  
    • SRP0422 PARP5A active human recombinant, expressed in baculovirus infected Sf9 cells, ≥30% (SDS-PAGE) New  
    • 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) New 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.
    • S8951 SR11237 ≥98% (HPLC) SR11237 is a selective pan retinoid X receptor (RXR) agonist with no retinoid A receptor (RAR) activity.
    • SML0636 SR1664 ≥98% (HPLC) New 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.
    • 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.
    • SML0510 S 26948 ≥98% (HPLC) New 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.
    • 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.
    • 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.
    • S1320 SR-202 ≥98% (HPLC), crystalline SR-202 is a selective PPARγ antagonist. Improves insulin sensitivity in diabetic mice.
    • 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.
    • T1698 Tetradecylthioacetic acid ≥97% (NMR) PPARα agonist; activation in ranking order: PPARδ > PPARα > PPARγ
    • T2573 Troglitazone ≥98% (HPLC) PPARγ agonist; anti-diabetic thiazolidinedione (TZD) with anti-inflammatory and anti-tumor activity; induces apoptosis via a p53 pathway.
    • 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.