Article
Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant.
Journal of medicinal chemistry - 24 Jun 2010
Huang Wei-Sheng, Metcalf Chester A, Sundaramoorthi Raji, Wang Yihan, Zou Dong, Thomas R Mathew, Zhu Xiaotian, Cai Lisi, Wen David, Liu Shuangying, Romero Jan, Qi Jiwei, Chen Ingrid, Banda Geetha, Lentini Scott P, Das Sasmita, Xu Qihong, Keats Jeff, Wang Frank, Wardwell Scott, Ning Yaoyu, Snodgrass Joseph T, Broudy Marc I, Russian Karin, Zhou Tianjun, Commodore Lois, Narasimhan Narayana I, Mohemmad Qurish K, Iuliucci John, Rivera Victor M, Dalgarno David C, Sawyer Tomi K, Clackson Tim, Shakespeare William C
Abstract excerpt
In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of Ile315 side...
Read the complete abstract on PubMedTopics
Share this publication in a Topic to start or enrich a Post.