mouse pparγ

Pioglitazone hydrochloride (AD 4833) 是一种选择性PPARγ激动剂，高亲和力结合到 PPARγ 配体结合域。作用于人和鼠 PPARγ，EC50分别为 0.93 和 0.99 μM。它是一种口服活性噻唑烷二酮的盐酸盐，具有抗糖尿病特性和潜在的抗肿瘤活性。

Pioglitazone (U 72107) 是一种胰岛素增敏剂和噻唑烷二酮，适用于治疗 2 型糖尿病。它是一种选择性PPARγ激动剂，高亲和力结合到 PPARγ 配体结合域，作用于人和鼠 PPARγ的EC50分别为 0.93 和 0.99 μM。

BAY-4931 是一种有效的、共价的、选择性的 PPARγ反向激动剂，IC50为 0.17 nM。

PPARγ agonist16 (Compound 4G) 是一种PPARγ激动剂，能够竞争性结合PPARγ的LBD结构域，其IC50为1790 nM。此化合物在小鼠模型中抑制耳朵肿胀，并在Streptozotocin诱导的小鼠糖尿病模型中展现抗高血糖作用。

PPARγmodulator-2 (Compound (R)-2n) 是一种PPARγ的可逆调节剂，能够抑制PPARγ配体结合域 (LBD)，其IC50为41 nM。PPARγmodulator-2 可降低血糖水平，改善葡萄糖耐受性和胰岛素耐受性，并在 db db 小鼠模型中展示出抗糖尿病活性。

PPARα δ agonist 3 (Compound 8) 是一种口服有效的PPAR激动剂，能够激活PPARα、PPARδ和PPARγ，其EC50值分别为5.6、3.4和1278 nM。在小鼠的ANIT或CDCA诱导的胆汁淤积性肝病模型中，PPARα δ agonist 3 显示出抗胆汁淤积的活性。

LT175 是一种双重PPARα γ配体，具有强大的胰岛素增敏作用和降低的脂肪生成特性。LT175是口服有效 PPARγ 的部分激动剂 (hPPARα:EC50=0.22 μM; mPPARα:EC50=0.26 μM; hPPARγ:EC50=0.48 μM)。LT175 与 PPARγ 相互作用并影响辅助调节因子环 AMP 反应元件结合蛋白结合蛋白和核辅助抑制因子 1 (NCoR1) 的募集。LT175 在“二苯口袋”的疏水区域中与 PPARγ 相互作用。

GW 9578 是一种具有选择性和有效性的 PPARα 激动剂 ，具有有效的降脂活性，可用于研究牛皮癣，关节炎，脱发，哮喘和I型糖尿病。

SR 1903 is a modulator of retinoic acid receptor-related orphan receptor γ (RORγ) and liver X receptor (LXR).1 It is an inverse agonist of RORγ (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor γ (PPARγ; IC50 = 209 nM) but does not activate it. SR 1903 (10 μM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity.References1. Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019). SR 1903 is a modulator of retinoic acid receptor-related orphan receptor γ (RORγ) and liver X receptor (LXR).1 It is an inverse agonist of RORγ (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor γ (PPARγ; IC50 = 209 nM) but does not activate it. SR 1903 (10 μM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity. References1. Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019).

ZLY032 is a dual agonist of free fatty acid receptor 1 (FFAR1 GPR40; EC50= 68 nM in a FLIPR assay) and peroxisome proliferator-activated receptor δ (PPARδ; EC50= 102 nM in a reporter assay).1It is selective for FFAR1 and PPARδ over PPARα and PPARγ (EC50s = >10 μM for both). ZLY032 (40 mg kg, twice per day) reduces blood glucose levels in an oral glucose tolerance test and decreases plasma total cholesterol and triglyceride levels in theob obmouse model of metabolic disease.2It reduces hepatic steatosis and plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in a mouse model of non-alcoholic steatohepatitis (NASH) induced by a methionine and choline-deficient diet at the same dose. 1.Li, Z., Chen, Y., Zhou, Z., et al.Discovery of first-in-class thiazole-based dual FFA1 PPARδ agonists as potential anti-diabetic agentsEur. J. Med. Chem.164352-365(2019) 2.Li, Z., Zhou, Z., Hu, L., et al.ZLY032, the first-in-class dual FFA1 PPARδ agonist, improves glucolipid metabolism and alleviates hepatic fibrosisPharmacol Res.159105035(2020)

Pioglitazone potassium (U 72107) is an orally active and selective agonist of peroxisome proliferator-activated receptor gamma (PPARγ). It demonstrates high affinity binding to the ligand-binding domain of PPARγ, with an EC50 of 0.93 μM and 0.99 μM for human and mouse PPARγ, respectively. Pioglitazone potassium has applications in diabetes research [2] [3] [4].

GSK1820795A 作为替米沙坦类似物是hGPR132a 的选择性拮抗剂。GSK1820795A 阻断了 N-acylamides 对表达hGPR132a 的酵母细胞的活化。GSK1820795A 也是血管紧张素 II 拮抗剂和部分PPARγ激动剂 (compound 38) 。

Norbixin是一种在B. orellana中发现的类胡萝卜素，具有多样的生物活性。在无细胞测试中，它与过氧化物酶体增殖物激活受体γ (PPARγ)结合（Ki = 1.15 µM）。在心脑血管代谢综合征大鼠模型中，Norbixin (47.7 mg/kg) 能够减轻高血糖、高胰岛素血症和胰岛素抗性，降低血清脂质水平及心脏中硫代巴比妥酸反应性物质（TBARS）和谷胱甘肽（GSH）的水平。在胆固醇诱导的动脉粥样硬化兔模型中，它降低氧化型LDL和主动脉蛋白氧化水平，并减少动脉粥样硬化面积。Norbixin（每天0.1和1 mg/kg）减少汞诱导的大鼠肝细胞和白细胞DNA损伤。此外，它还能预防与年龄相关的黄斑变性（AMD）Abca4-/- Rdh8-/-小鼠模型中的光感受器退化。

15-deoxy-Δ12,14-Prostaglandin D2 (15-deoxy-Δ12,14-PGD2) is a PGD2 metabolite functioning as an agonist for the PGD2 receptor 2 (DP2), with a binding affinity (Ki) of 50 nM for the mouse DP2 receptor expressed in HEK293 cell membranes. It activates eosinophils with an EC50 of 8 nM and enhances the recruitment of steroid receptor coactivator-1 (SRC-1) to peroxisome proliferator-activated receptor γ (PPARγ), initiating PPARγ-mediated transcription at 5 µM concentration. Furthermore, it exhibits cytotoxicity towards L1210 murine leukemia cells with an IC50 of 0.3 µg ml and displays weaker inhibition of ADP-induced platelet aggregation than PGD2, with an IC50 of 320 ng ml.

YGT-31作为PPARγ调节剂,其IC50值为1.72 μM,Ki值为0.62 μM.通过抑制CDK5介导的PPARγ-Ser273的磷酸化,YGT-31能在db db小鼠的2型糖尿病模型中显著降低血糖并改善胰岛素抵抗.此外,YGT-31在小鼠的非酒精性脂肪性肝病(NAFLD)模型中也展示了抗肝脂肪变性的效果.

ST-CY14 是一种 Nur77-PPARγ 相互作用的抑制剂，其 EC50 为 3.15 μM，能够与 Nur77 结合（Kd=32 nM），阻止 Nur77 被 PPARγ 泛素化和降解，从而减少脂肪酸摄取和线粒体呼吸，抑制 CD36 和 FABP4 的转录。在 MCF7 和 MDA-MB-231 癌细胞中，ST-CY14 能够阻碍其增殖和迁移。此外，ST-CY14 在小鼠模型中可抑制肿瘤生长及骨转移。