作者
Andrew J Souers, Joel D Leverson, Erwin R Boghaert, Scott L Ackler, Nathaniel D Catron, Jun Chen, Brian D Dayton, Hong Ding, Sari H Enschede, Wayne J Fairbrother, David CS Huang, Sarah G Hymowitz, Sha Jin, Seong Lin Khaw, Peter J Kovar, Lloyd T Lam, Jackie Lee, Heather L Maecker, Kennan C Marsh, Kylie D Mason, Michael J Mitten, Paul M Nimmer, Anatol Oleksijew, Chang H Park, Cheol-Min Park, Darren C Phillips, Andrew W Roberts, Deepak Sampath, John F Seymour, Morey L Smith, Gerard M Sullivan, Stephen K Tahir, Chris Tse, Michael D Wendt, Yu Xiao, John C Xue, Haichao Zhang, Rod A Humerickhouse, Saul H Rosenberg, Steven W Elmore
发表日期
2013/2
期刊
Nature medicine
卷号
19
期号
2
页码范围
202-208
出版商
Nature Publishing Group US
简介
Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2–like 1 (BCL-XL), which has shown clinical efficacy in some BCL-2–dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-XL inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2–selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2–dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in …
学术搜索中的文章
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
AJ Souers, JD Leverson, ER Boghaert, SL Ackler… - Nature medicine, 2013