Article
Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants.
Journal of medicinal chemistry - 10 Mar 2016
Cheng Hengmiao, Nair Sajiv K, Murray Brion W, Almaden Chau, Bailey Simon, Baxi Sangita, Behenna Doug, Cho-Schultz Sujin, Dalvie Deepak, Dinh Dac M, Edwards Martin P, Feng Jun Li, Ferre Rose Ann, Gajiwala Ketan S, Hemkens Michelle D, Jackson-Fisher Amy, Jalaie Mehran, Johnson Ted O, Kania Robert S, Kephart Susan, Lafontaine Jennifer, Lunney Beth, Liu Kevin K-C, Liu Zhengyu, Matthews Jean, Nagata Asako, Niessen Sherry, Ornelas Martha A, Orr Suvi T M, Pairish Mason, Planken Simon, Ren Shijian, Richter Daniel, Ryan Kevin, Sach Neal, Shen Hong, Smeal Tod, Solowiej Jim, Sutton Scott, Tran Khanh, Tseng Elaine, Vernier William, Walls Marlena, Wang Shuiwang, Weinrich Scott L, Xin Shuibo, Xu Haiwei, Yin Min-Jean, Zientek Michael, Zhou Ru, Kath John C
Abstract excerpt
First generation EGFR TKIs (gefitinib, erlotinib) provide significant clinical benefit for NSCLC cancer patients with oncogenic EGFR mutations. Ultimately, these patients' disease progresses, often driven by a second-site mutation in the EGFR kinase domain (T790M). Another liability of the first generation drugs is severe adverse events driven by inhibition of WT EGFR. As such, our goal was to develop a highly...
Read the complete abstract on PubMed