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Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors.
Estrada AA, Chan BK, Baker-Glenn C, Beresford A, Burdick DJ, Chambers M, Chen H, Dominguez SL, Dotson J, Drummond J, Flagella M, Fuji R, Gill A, Halladay J, Harris SF, Heffron TP, Kleinheinz T, Lee DW, Le Pichon CE, Liu X, Lyssikatos JP, Medhurst AD, Moffat JG, Nash K, Scearce-Levie K, Sheng Z, Shore DG, Wong S, Zhang S, Zhang X, Zhu H, Sweeney ZK. Estrada AA, et al. Among authors: zhang s, zhang x. J Med Chem. 2014 Feb 13;57(3):921-36. doi: 10.1021/jm401654j. Epub 2014 Jan 15. J Med Chem. 2014. PMID: 24354345
Preclinical assessment of the absorption and disposition of the phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor GDC-0980 and prediction of its pharmacokinetics and efficacy in human.
Salphati L, Pang J, Plise EG, Lee LB, Olivero AG, Prior WW, Sampath D, Wong S, Zhang X. Salphati L, et al. Among authors: zhang x. Drug Metab Dispos. 2012 Sep;40(9):1785-96. doi: 10.1124/dmd.112.046052. Epub 2012 Jun 13. Drug Metab Dispos. 2012. PMID: 22696419
The design and identification of brain penetrant inhibitors of phosphoinositide 3-kinase α.
Heffron TP, Salphati L, Alicke B, Cheong J, Dotson J, Edgar K, Goldsmith R, Gould SE, Lee LB, Lesnick JD, Lewis C, Ndubaku C, Nonomiya J, Olivero AG, Pang J, Plise EG, Sideris S, Trapp S, Wallin J, Wang L, Zhang X. Heffron TP, et al. Among authors: zhang x. J Med Chem. 2012 Sep 27;55(18):8007-20. doi: 10.1021/jm300867c. Epub 2012 Sep 11. J Med Chem. 2012. PMID: 22946614
Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors.
Estrada AA, Liu X, Baker-Glenn C, Beresford A, Burdick DJ, Chambers M, Chan BK, Chen H, Ding X, DiPasquale AG, Dominguez SL, Dotson J, Drummond J, Flagella M, Flynn S, Fuji R, Gill A, Gunzner-Toste J, Harris SF, Heffron TP, Kleinheinz T, Lee DW, Le Pichon CE, Lyssikatos JP, Medhurst AD, Moffat JG, Mukund S, Nash K, Scearce-Levie K, Sheng Z, Shore DG, Tran T, Trivedi N, Wang S, Zhang S, Zhang X, Zhao G, Zhu H, Sweeney ZK. Estrada AA, et al. Among authors: zhang s, zhang x. J Med Chem. 2012 Nov 26;55(22):9416-33. doi: 10.1021/jm301020q. Epub 2012 Oct 15. J Med Chem. 2012. PMID: 22985112
Targeting the PI3K pathway in the brain--efficacy of a PI3K inhibitor optimized to cross the blood-brain barrier.
Salphati L, Heffron TP, Alicke B, Nishimura M, Barck K, Carano RA, Cheong J, Edgar KA, Greve J, Kharbanda S, Koeppen H, Lau S, Lee LB, Pang J, Plise EG, Pokorny JL, Reslan HB, Sarkaria JN, Wallin JJ, Zhang X, Gould SE, Olivero AG, Phillips HS. Salphati L, et al. Among authors: zhang x. Clin Cancer Res. 2012 Nov 15;18(22):6239-48. doi: 10.1158/1078-0432.CCR-12-0720. Epub 2012 Sep 19. Clin Cancer Res. 2012. PMID: 22992516
Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations.
Sheng Z, Zhang S, Bustos D, Kleinheinz T, Le Pichon CE, Dominguez SL, Solanoy HO, Drummond J, Zhang X, Ding X, Cai F, Song Q, Li X, Yue Z, van der Brug MP, Burdick DJ, Gunzner-Toste J, Chen H, Liu X, Estrada AA, Sweeney ZK, Scearce-Levie K, Moffat JG, Kirkpatrick DS, Zhu H. Sheng Z, et al. Among authors: zhang s, zhang x. Sci Transl Med. 2012 Dec 12;4(164):164ra161. doi: 10.1126/scitranslmed.3004485. Sci Transl Med. 2012. PMID: 23241745
Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR.
Heffron TP, Ndubaku CO, Salphati L, Alicke B, Cheong J, Drobnick J, Edgar K, Gould SE, Lee LB, Lesnick JD, Lewis C, Nonomiya J, Pang J, Plise EG, Sideris S, Wallin J, Wang L, Zhang X, Olivero AG. Heffron TP, et al. Among authors: zhang x. ACS Med Chem Lett. 2016 Feb 16;7(4):351-6. doi: 10.1021/acsmedchemlett.6b00005. eCollection 2016 Apr 14. ACS Med Chem Lett. 2016. PMID: 27096040 Free PMC article.
Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma.
Salphati L, Alicke B, Heffron TP, Shahidi-Latham S, Nishimura M, Cao T, Carano RA, Cheong J, Greve J, Koeppen H, Lau S, Lee LB, Nannini-Pepe M, Pang J, Plise EG, Quiason C, Rangell L, Zhang X, Gould SE, Phillips HS, Olivero AG. Salphati L, et al. Among authors: zhang x. Drug Metab Dispos. 2016 Dec;44(12):1881-1889. doi: 10.1124/dmd.116.071423. Epub 2016 Sep 16. Drug Metab Dispos. 2016. PMID: 27638506
165,625 results
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