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81 results

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Page 1
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. J Med Chem. 2012 Nov 26;55(22):9416-33. doi: 10.1021/jm301020q. Epub 2012 Oct 15. J Med Chem. 2012. PMID: 22985112
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. Sci Transl Med. 2012 Dec 12;4(164):164ra161. doi: 10.1126/scitranslmed.3004485. Sci Transl Med. 2012. PMID: 23241745
Mechanistic pharmacokinetic-pharmacodynamic modeling of BACE1 inhibition in monkeys: development of a predictive model for amyloid precursor protein processing.
Liu X, Wong H, Scearce-Levie K, Watts RJ, Coraggio M, Shin YG, Peng K, Wildsmith KR, Atwal JK, Mango J, Schauer SP, Regal K, Hunt KW, Thomas AA, Siu M, Lyssikatos J, Deshmukh G, Hop CE. Liu X, et al. Drug Metab Dispos. 2013 Jul;41(7):1319-28. doi: 10.1124/dmd.112.050864. Epub 2013 Apr 12. Drug Metab Dispos. 2013. PMID: 23584887
Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier.
Couch JA, Yu YJ, Zhang Y, Tarrant JM, Fuji RN, Meilandt WJ, Solanoy H, Tong RK, Hoyte K, Luk W, Lu Y, Gadkar K, Prabhu S, Ordonia BA, Nguyen Q, Lin Y, Lin Z, Balazs M, Scearce-Levie K, Ernst JA, Dennis MS, Watts RJ. Couch JA, et al. Sci Transl Med. 2013 May 1;5(183):183ra57, 1-12. doi: 10.1126/scitranslmed.3005338. Sci Transl Med. 2013. PMID: 23636093
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. J Med Chem. 2014 Feb 13;57(3):921-36. doi: 10.1021/jm401654j. Epub 2014 Jan 15. J Med Chem. 2014. PMID: 24354345
Discovery of 7-tetrahydropyran-2-yl chromans: β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors that reduce amyloid β-protein (Aβ) in the central nervous system.
Thomas AA, Hunt KW, Volgraf M, Watts RJ, Liu X, Vigers G, Smith D, Sammond D, Tang TP, Rhodes SP, Metcalf AT, Brown KD, Otten JN, Burkard M, Cox AA, Do MK, Dutcher D, Rana S, DeLisle RK, Regal K, Wright AD, Groneberg R, Scearce-Levie K, Siu M, Purkey HE, Lyssikatos JP, Gunawardana IW. Thomas AA, et al. J Med Chem. 2014 Feb 13;57(3):878-902. doi: 10.1021/jm401635n. Epub 2014 Jan 22. J Med Chem. 2014. PMID: 24397738
Discovery of a Highly Selective, Brain-Penetrant Aminopyrazole LRRK2 Inhibitor.
Chan BK, Estrada AA, Chen H, Atherall J, Baker-Glenn C, Beresford A, Burdick DJ, Chambers M, Dominguez SL, Drummond J, Gill A, Kleinheinz T, Le Pichon CE, Medhurst AD, Liu X, Moffat JG, Nash K, Scearce-Levie K, Sheng Z, Shore DG, Van de Poël H, Zhang S, Zhu H, Sweeney ZK. Chan BK, et al. ACS Med Chem Lett. 2012 Nov 23;4(1):85-90. doi: 10.1021/ml3003007. eCollection 2013 Jan 10. ACS Med Chem Lett. 2012. PMID: 24900567 Free PMC article.
Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models.
Patel S, Cohen F, Dean BJ, De La Torre K, Deshmukh G, Estrada AA, Ghosh AS, Gibbons P, Gustafson A, Huestis MP, Le Pichon CE, Lin H, Liu W, Liu X, Liu Y, Ly CQ, Lyssikatos JP, Ma C, Scearce-Levie K, Shin YG, Solanoy H, Stark KL, Wang J, Wang B, Zhao X, Lewcock JW, Siu M. Patel S, et al. J Med Chem. 2015 Jan 8;58(1):401-18. doi: 10.1021/jm5013984. Epub 2014 Oct 23. J Med Chem. 2015. PMID: 25341110
81 results