2yfx

Publication Abstract from PubMed

Crizotinib (1), an ALK receptor tyrosine kinase inhibitor approved by the FDA in 2011, is efficacious in ALK and ROS positive patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine 8e which was potent across a broad panel of engineered ALK mutant cell lines, showed suitable pre-clinical PK and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

The design of potent and selective inhibitors to overcome clinical ALK mutations resistant to crizotinib.,Huang Q, Johnson TW, Bailey S, Brooun A, Bunker KD, Burke BJ, Collins MR, Cook A, Cui JJ, Dack KN, Deal JG, Deng YL, Dinh DM, Engstrom LD, He M, Hoffman J, Hoffman RL, Shen H, Johnson P, Kania RS, Lam H, Lam JL, Le P, Li Q, Lingardo L, Liu W, West Lu M, McTigue MA, Palmer CL, Richardson PF, Sach NW, Smeal T, Smith GL, Stewart AE, Timofeevski SL, Tsaparikos K, Wang H, Zhu H, Zhu J, Zou HY, Edwards M J Med Chem. 2014 Jan 16. PMID:24432909^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.