Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway.
Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway.
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DOI：
10.1016/j.bmc.2010.05.001
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发表时间：
2010-07-01
影响因子：
3.5
通讯作者：
Fujii, Naoaki
中科院分区：
文献类型：
--
作者：
Mahindroo, Neeraj;Connelly, Michele C.;Punchihewa, Chandanamali;Yang, Lei;Yan, Bing;Fujii, Naoaki
我们以前曾报道过小分子抑制剂Gli 1介导的转录，Hh途径的一个重要的下游元件。我们创造了以前化合物的新衍生物，旨在改善药物特性。新的化合物，酮洛芬和吲哚的酰胺共轭物，显示出抑制活性和膜通透性，同时也提高了微粒体稳定性。其中，33和42分别以2.6 μM和1.6 μM的IC 50抑制用Gli 1外源转染的C3 H10 T1/2细胞中的Gli-fluorescence报告基因，以及在内源性过表达Gli 1的Rh 30细胞中，对Gli 1的选择性高于Gli 2。
We have previously reported small-molecule inhibitors of Gli1-mediated transcription, an essential down-stream element of the Hh pathway. We created new derivatives of the previous compounds aiming to improve the druggable property. The new compounds, amide conjugates of ketoprofen and indole, showed inhibitory activity and membrane permeability, while also improving the microsome stability. Among them, 33 and 42 inhibited Gli-luciferase reporter in C3H10T1/2 cells that were exogenously transfected with Gli1 with 2.6 µM and 1.6 µM of IC50 respectively, and in Rh30 cells that endogenously overexpress Gli1, and was selective to Gli1 over Gli2.
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DOI：
10.1126/science.1179386
发表时间：
2009-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yauch RL;Dijkgraaf GJ;Alicke B;Januario T;Ahn CP;Holcomb T;Pujara K;Stinson J;Callahan CA;Tang T;Bazan JF;Kan Z;Seshagiri S;Hann CL;Gould SE;Low JA;Rudin CM;de Sauvage FJ
通讯作者：
de Sauvage FJ
影响因子：
2.7
作者：
Forbes, IT;Douglas, S;Thomas, DR
通讯作者：
Thomas, DR
影响因子：
4.8
作者：
Yoon, JW;Kita, Y;Iannaccone, P
通讯作者：
Iannaccone, P
影响因子：
7.3
作者：
Mahindroo N;Punchihewa C;Fujii N
通讯作者：
Fujii N
影响因子：
7.3
作者：
Wright, JL;Gregory, TF;Wise, LD
通讯作者：
Wise, LD