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223132-37-4

中文名稱 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-噻唑啉二酮
英文名稱 inolitazone
CAS 223132-37-4
分子式 C27H26N4O4S
分子量 502.58
MOL 文件 223132-37-4.mol
更新日期 2023/03/17 20:03:07
223132-37-4 結(jié)構(gòu)式 223132-37-4 結(jié)構(gòu)式

基本信息

中文別名
伊諾他酮
伊諾他酮二鹽酸鹽
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-噻唑啉二酮
英文別名
RS5444
CS-1166
Efatutazone
inolitazone
Inolitazone (CS-7017)
Inolitazone Efatutazone
5-[[4-[[6-(4-Amino-3,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-yl]methoxy]phenyl]methyl]-2,4-thiazolidinedione
2,4-Thiazolidinedione, 5-[[4-[[6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-yl]methoxy]phenyl]methyl]-
所屬類別
生物化工:激動(dòng)劑抑制劑

物理化學(xué)性質(zhì)

沸點(diǎn)765.7±60.0 °C(Predicted)
密度1.39
儲(chǔ)存條件-20°C儲(chǔ)存
溶解度DMSO
酸度系數(shù)(pKa)6.34±0.50(Predicted)
形態(tài)粉末

常見(jiàn)問(wèn)題列表

生物活性
Inolitazone(RS5444; CS-7017)是新型PPARγ高親和性激動(dòng)劑,EC50為rosiglitazone的五十分之一,對(duì)于不表達(dá)PPARγ的RIE細(xì)胞無(wú)抑制性。
靶點(diǎn)

PPARγ

體外研究

Inolitazone (RS5444) 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.

體內(nèi)研究

Inolitazone (RS5444) 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.

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