中文名称:

5-[[4-[[6-(4-氨基-3,5-二甲基苯氧基)-1-甲基-1H-苯并咪唑-2-基]甲氧基]苯基]甲基]-2,4-噻唑烷二酮二盐酸盐

中文同义词:

5-[[4-[[6-(4-氨基-3,5-二甲基苯氧基)-1-甲基-1H-苯并咪唑-2-基]甲氧基]苯基]甲基]-2,4-噻唑烷二酮二盐酸盐;PPARΓ激动剂(INOLITAZONE DIHYDROCHLORIDE)

英文名称:

CS 7017

英文同义词:

Inolitazone (CS-7017) dihydrochloride;RS5444 dihydrochloride;CS 7017;Inolitazone (dihydrochloride);5-[[4-[[6-(4-Amino-3,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-yl]methoxy]phenyl]methyl]-2,4-thiazolidinedione dihydrochloride;Inolitazone (CS-7017) 2HCl;5-[[4-[[6-(4-amino-3,5-dimethylphenoxy)-1-methylbenzimidazol-2-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione;EFATUTAZONE; CS-7017; RS5444; CS 7017; RS 5444

CAS号:

223132-38-5

分子式:

C27H28Cl2N4O4S

分子量:

575.50662

EINECS号:

相关类别:

细胞生物学试剂

Mol文件:

223132-38-5.mol

生物活性

Inolitazone dihydrochloride (Efatutazone dihydrochloride) 是一种高亲和力的 PPARγ 激动剂，活性依赖于 PPARγ，抑制生长，IC50 为 0.8 nM。

靶点

PPARγ

PPARγ

体外研究

Inolitazone dihydrochloride (Efatutazone dihydrochloride) upregulates the cell cycle kinase inhibitor, p21 WAF1/CIP1 . Silencing p21 WAF1/CIP1 rendered cells insensitive to Inolitazone. A 10 nM dose of Inolitazone activates PPARγ:RXRα-dependent transcription as demonstrated in a transient transfection assay utilizing a PPRE response element fused to a luciferase reporter gene (PPRE3-tk-luc). DRO cells are treated in culture with Inolitazone, Rosiglitazone, or Troglitazone at the indicated concentrations. DRO cells are transiently transfected with PPRE3-tk-luc to examine effective concentrations at which EC 50 occurs. The EC 50 s are 1 nM (Inolitazone), 65 nM (Rosiglitazone) and 631 nM (Troglitazone). Similarly, the calculated inhibitory concentration at IC 50 is 0.8 nM for Inolitazone, 75 nM for Rosiglitazone, and 1412 nM for Troglitazone. Inolitazone specifically activates PPARγ, but not PPARα or PPARδ. Exposure of 10 nM Inolitazone following transient transfection with the appropriate PPAR isoform (γ, α, or δ) and PPAR response element linked to a luciferase reporter in RIE rat small intestinal cell line, which does not express PPARs, yields increased luciferase activity only in the presence of PPARγ and PPRE3-tk-luc. DRO cells are growth inhibited by 10 nM Inolitazone (RS5444) through a PPARγ-dependent mechanism.

体内研究

Inolitazone dihydrochloride (Efatutazone dihydrochloride) plus Paclitaxel demonstrate additive antiproliferative activity in cell culture and minimal ATC tumor growth. When Inolitazone is administered in the diet to athymic nude mice prior to DRO tumor cell implantation, tumor growth is inhibited in a dose responsive fashion. At the highest dose, 0.025% Inolitazone inhibits growth on day 32 by 94.4% as compared to that of control. In this treatment group, five of 10 animals do not develop demonstrable tumors. In the 0.0025% treatment group, tumor growth is inhibited by 62.3% compared to that of control on day 32 while the 0.00025% dose demonstrated no growth inhibitory activity as compared to control. Tumors is nest allowed to establish in the mouse and began 0.025% Inolitazone treatment of mice 1 week after DRO or ARO tumor cell implantation. Inolitazone treated animals demonstrate tumor growth inhibition of 68.9% in DRO tumors and 48.3% in ARO tumors as compared to that of their respective controls on day 35.