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 PPARγ激动剂，作用于人和鼠 PPARγ 的 EC50 分别为 0.93 和 0.99 μM，具有选择性、口服活性。Pioglitazone 可用于糖尿病研究。

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。

DN-108 是一种噻唑烷二酮类衍生物，具有口服活性的过氧化物酶体增殖物激活受体 γ (PPARγ) 激动剂，显示出抗糖尿病的特性。DN-108 能改善糖尿病小鼠模型中的高血糖、高甘油三酯血症和高胰岛素血症。此外，DN-108 还能增强组织葡萄糖摄取，例如增加 L6 肌肉细胞对 2-脱氧葡萄糖的摄取，并抑制脂肪酸合成酶的活性。DN-108 在 2 型糖尿病研究中具有潜在应用。

ABP/PPAR modulator 1 是一种口服活性的FABP和PPAR多重调节剂，其FABP1和FABP4的IC50分别为0.65 μM和1.08 μM，PPARα、PPARγ和PPARδ的EC50分别为9.19 μM、2.20 μM和1.58 μM。它在改善代谢功能障碍相关脂肪性肝炎 (MASH) 方面表现出强效活性。在WD + Carbon tetrachloride诱导的MASH小鼠模型中，ABP/PPAR modulator 1 剂量依赖性地改善脂肪肝的多种病理特征。

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) 。

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。

Falcarindiol是一种具有口服活性的天然聚乙炔化合物，具有抗炎和抗增殖的特性，能够抑制LPS诱导的小鼠巨噬细胞中NO生成，还能降低JAK1和JAK2的酪氨酸磷酸化，调节STAT1的核易位，从而抑制iNOS的表达。

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。