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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: zhu h. 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. Among authors: zhu h. Sci Transl Med. 2012 Dec 12;4(164):164ra161. doi: 10.1126/scitranslmed.3004485. Sci Transl Med. 2012. PMID: 23241745
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: zhu h. 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 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. Among authors: zhu h. 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.
Effect of selective LRRK2 kinase inhibition on nonhuman primate lung.
Fuji RN, Flagella M, Baca M, Baptista MA, Brodbeck J, Chan BK, Fiske BK, Honigberg L, Jubb AM, Katavolos P, Lee DW, Lewin-Koh SC, Lin T, Liu X, Liu S, Lyssikatos JP, O'Mahony J, Reichelt M, Roose-Girma M, Sheng Z, Sherer T, Smith A, Solon M, Sweeney ZK, Tarrant J, Urkowitz A, Warming S, Yaylaoglu M, Zhang S, Zhu H, Estrada AA, Watts RJ. Fuji RN, et al. Among authors: zhu h. Sci Transl Med. 2015 Feb 4;7(273):273ra15. doi: 10.1126/scitranslmed.aaa3634. Sci Transl Med. 2015. PMID: 25653221
Discovery of potent azaindazole leucine-rich repeat kinase 2 (LRRK2) inhibitors possessing a key intramolecular hydrogen bond - Part 2.
Shore DGM, Sweeney ZK, Beresford A, Chan BK, Chen H, Drummond J, Gill A, Kleinheinz T, Liu X, Medhurst AD, McIver EG, Moffat JG, Zhu H, Estrada AA. Shore DGM, et al. Among authors: zhu h. Bioorg Med Chem Lett. 2019 Feb 15;29(4):674-680. doi: 10.1016/j.bmcl.2018.10.017. Epub 2018 Oct 12. Bioorg Med Chem Lett. 2019. PMID: 30522953
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