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Page 1
Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK).
Cui JJ, Tran-Dubé M, Shen H, Nambu M, Kung PP, Pairish M, Jia L, Meng J, Funk L, Botrous I, McTigue M, Grodsky N, Ryan K, Padrique E, Alton G, Timofeevski S, Yamazaki S, Li Q, Zou H, Christensen J, Mroczkowski B, Bender S, Kania RS, Edwards MP. Cui JJ, et al. J Med Chem. 2011 Sep 22;54(18):6342-63. doi: 10.1021/jm2007613. Epub 2011 Aug 18. J Med Chem. 2011. PMID: 21812414
Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor (c-MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (PF-04217903) for the treatment of cancer.
Cui JJ, McTigue M, Nambu M, Tran-Dubé M, Pairish M, Shen H, Jia L, Cheng H, Hoffman J, Le P, Jalaie M, Goetz GH, Ryan K, Grodsky N, Deng YL, Parker M, Timofeevski S, Murray BW, Yamazaki S, Aguirre S, Li Q, Zou H, Christensen J. Cui JJ, et al. J Med Chem. 2012 Sep 27;55(18):8091-109. doi: 10.1021/jm300967g. Epub 2012 Sep 10. J Med Chem. 2012. PMID: 22924734
Lessons from (S)-6-(1-(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (PF-04254644), an inhibitor of receptor tyrosine kinase c-Met with high protein kinase selectivity but broad phosphodiesterase family inhibition leading to myocardial degeneration in rats.
Cui JJ, Shen H, Tran-Dubé M, Nambu M, McTigue M, Grodsky N, Ryan K, Yamazaki S, Aguirre S, Parker M, Li Q, Zou H, Christensen J. Cui JJ, et al. J Med Chem. 2013 Sep 12;56(17):6651-65. doi: 10.1021/jm400926x. Epub 2013 Aug 29. J Med Chem. 2013. PMID: 23944843
Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib.
Huang Q, Johnson TW, Bailey S, Brooun A, Bunker KD, Burke BJ, Collins MR, Cook AS, Cui JJ, Dack KN, Deal JG, Deng YL, Dinh D, Engstrom LD, He M, Hoffman J, Hoffman RL, Johnson PS, Kania RS, Lam H, Lam JL, Le PT, Li Q, Lingardo L, Liu W, Lu MW, McTigue M, Palmer CL, Richardson PF, Sach NW, Shen H, Smeal T, Smith GL, Stewart AE, Timofeevski S, Tsaparikos K, Wang H, Zhu H, Zhu J, Zou HY, Edwards MP. Huang Q, et al. J Med Chem. 2014 Feb 27;57(4):1170-87. doi: 10.1021/jm401805h. Epub 2014 Feb 6. J Med Chem. 2014. PMID: 24432909 Free article.
Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations.
Johnson TW, Richardson PF, Bailey S, Brooun A, Burke BJ, Collins MR, Cui JJ, Deal JG, Deng YL, Dinh D, Engstrom LD, He M, Hoffman J, Hoffman RL, Huang Q, Kania RS, Kath JC, Lam H, Lam JL, Le PT, Lingardo L, Liu W, McTigue M, Palmer CL, Sach NW, Smeal T, Smith GL, Stewart AE, Timofeevski S, Zhu H, Zhu J, Zou HY, Edwards MP. Johnson TW, et al. J Med Chem. 2014 Jun 12;57(11):4720-44. doi: 10.1021/jm500261q. Epub 2014 Jun 3. J Med Chem. 2014. PMID: 24819116
PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.
Zou HY, Li Q, Engstrom LD, West M, Appleman V, Wong KA, McTigue M, Deng YL, Liu W, Brooun A, Timofeevski S, McDonnell SR, Jiang P, Falk MD, Lappin PB, Affolter T, Nichols T, Hu W, Lam J, Johnson TW, Smeal T, Charest A, Fantin VR. Zou HY, et al. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3493-8. doi: 10.1073/pnas.1420785112. Epub 2015 Mar 2. Proc Natl Acad Sci U S A. 2015. PMID: 25733882 Free PMC article.
45 results