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Page 1
Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson's disease.
Jennings D, Huntwork-Rodriguez S, Henry AG, Sasaki JC, Meisner R, Diaz D, Solanoy H, Wang X, Negrou E, Bondar VV, Ghosh R, Maloney MT, Propson NE, Zhu Y, Maciuca RD, Harris L, Kay A, LeWitt P, King TA, Kern D, Ellenbogen A, Goodman I, Siderowf A, Aldred J, Omidvar O, Masoud ST, Davis SS, Arguello A, Estrada AA, de Vicente J, Sweeney ZK, Astarita G, Borin MT, Wong BK, Wong H, Nguyen H, Scearce-Levie K, Ho C, Troyer MD. Jennings D, et al. Among authors: scearce levie k. Sci Transl Med. 2022 Jun 8;14(648):eabj2658. doi: 10.1126/scitranslmed.abj2658. Epub 2022 Jun 8. Sci Transl Med. 2022. PMID: 35675433
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
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 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
Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease.
Le Pichon CE, Meilandt WJ, Dominguez S, Solanoy H, Lin H, Ngu H, Gogineni A, Sengupta Ghosh A, Jiang Z, Lee SH, Maloney J, Gandham VD, Pozniak CD, Wang B, Lee S, Siu M, Patel S, Modrusan Z, Liu X, Rudhard Y, Baca M, Gustafson A, Kaminker J, Carano RAD, Huang EJ, Foreman O, Weimer R, Scearce-Levie K, Lewcock JW. Le Pichon CE, et al. Sci Transl Med. 2017 Aug 16;9(403):eaag0394. doi: 10.1126/scitranslmed.aag0394. Sci Transl Med. 2017. PMID: 28814543
DNL104, a Centrally Penetrant RIPK1 Inhibitor, Inhibits RIP1 Kinase Phosphorylation in a Randomized Phase I Ascending Dose Study in Healthy Volunteers.
Grievink HW, Heuberger JAAC, Huang F, Chaudhary R, Birkhoff WAJ, Tonn GR, Mosesova S, Erickson R, Moerland M, Haddick PCG, Scearce-Levie K, Ho C, Groeneveld GJ. Grievink HW, et al. Clin Pharmacol Ther. 2020 Feb;107(2):406-414. doi: 10.1002/cpt.1615. Epub 2019 Sep 25. Clin Pharmacol Ther. 2020. PMID: 31437302 Clinical Trial.
80 results