发明名称 |
BAX-activating cancer therapeutics |
摘要 |
The pro-apoptotic Bcl-2 protein Bax initiates apoptosis in almost all apoptotic paradigms. Agents facilitating disruptive Bax insertion into mitochondrial membranes have potential as cancer therapeutics. Small molecule compounds associating with the hydrophobic groove of the pro-apoptotic Bcl-2 protein Bax have been identified and found to promote Bax-dependent, but not Bak-dependent, apoptosis. The compounds alter Bax protein stability in vitro and promote Bax insertion into mitochondria, leading to Bax-dependent mitochondrial outer membrane permeabilization and apoptosis. The compounds activating the pro-apoptotic Bcl-2 protein Bax inhibit the growth of tumors by inducing apoptosis. Pharmaceutical compositions comprising the compounds that activate Bax and induce Bax-dependent apoptosis are useful as anti-cancer therapeutic agents alone or with other anti-cancer agents. Methods for inducing apoptosis and for treating cancer involve administering the compounds to a patient in need thereof. |
申请公布号 |
US9561215(B2) |
申请公布日期 |
2017.02.07 |
申请号 |
US201514589050 |
申请日期 |
2015.01.05 |
申请人 |
THE UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION INC. |
发明人 |
Li Chi;Trent John O. |
分类号 |
A61K31/437;A61K31/282;A61K31/495 |
主分类号 |
A61K31/437 |
代理机构 |
Thrive IP |
代理人 |
Thrive IP ;Stipkala Jeremy M. |
主权项 |
1. A pharmaceutical composition comprising:
an effective amount of 1-{[5 -(3,4-dimethylbenzyl)-1-(3-methoxybenzyl)-4,5,6,7-tetrahydro-1H -pyrazolo[4,3-c]pyridin-3-yl]carbonyl}-3-piperidinol, at least one pharmaceutically-acceptable salt thereof, or a combination thereof, and at least one pharmaceutically-acceptable excipient. |
地址 |
Louisville KY US |