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Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients.
Vissers MFJM, Heuberger JAAC, Groeneveld GJ, Oude Nijhuis J, De Deyn PP, Hadi S, Harris J, Tsai RM, Cruz-Herranz A, Huang F, Tong V, Erickson R, Zhu Y, Scearce-Levie K, Hsiao-Nakamoto J, Tang X, Chang M, Fox BM, Estrada AA, Pomponio RJ, Alonso-Alonso M, Zilberstein M, Atassi N, Troyer MD, Ho C. Vissers MFJM, et al. Among authors: estrada aa. Clin Transl Sci. 2022 Aug;15(8):2010-2023. doi: 10.1111/cts.13317. Epub 2022 Jun 1. Clin Transl Sci. 2022. PMID: 35649245 Free PMC article. Clinical Trial.
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: estrada aa. 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. 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 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. Among authors: estrada aa. J Med Chem. 2015 Jan 8;58(1):401-18. doi: 10.1021/jm5013984. Epub 2014 Oct 23. J Med Chem. 2015. PMID: 25341110
LRRK2 inhibitors induce reversible changes in nonhuman primate lungs without measurable pulmonary deficits.
Baptista MAS, Merchant K, Barrett T, Bhargava S, Bryce DK, Ellis JM, Estrada AA, Fell MJ, Fiske BK, Fuji RN, Galatsis P, Henry AG, Hill S, Hirst W, Houle C, Kennedy ME, Liu X, Maddess ML, Markgraf C, Mei H, Meier WA, Needle E, Ploch S, Royer C, Rudolph K, Sharma AK, Stepan A, Steyn S, Trost C, Yin Z, Yu H, Wang X, Sherer TB. Baptista MAS, et al. Among authors: estrada aa. Sci Transl Med. 2020 Apr 22;12(540):eaav0820. doi: 10.1126/scitranslmed.aav0820. Sci Transl Med. 2020. PMID: 32321864
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: estrada aa. 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 DNL343: A Potent, Selective, and Brain-Penetrant eIF2B Activator Designed for the Treatment of Neurodegenerative Diseases.
Craig RA 2nd, De Vicente J, Estrada AA, Feng JA, Lexa KW, Canet MJ, Dowdle WE, Erickson RI, Flores BN, Haddick PCG, Kane LA, Lewcock JW, Moerke NJ, Poda SB, Sweeney Z, Takahashi RH, Tong V, Wang J, Yulyaningsih E, Solanoy H, Scearce-Levie K, Sanchez PE, Tang L, Xu M, Zhang R, Osipov M. Craig RA 2nd, et al. Among authors: estrada aa. J Med Chem. 2024 Apr 11;67(7):5758-5782. doi: 10.1021/acs.jmedchem.3c02422. Epub 2024 Mar 21. J Med Chem. 2024. PMID: 38511649
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
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: estrada aa. 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.
Selective Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12) with Activity in a Model of Alzheimer's Disease.
Patel S, Meilandt WJ, Erickson RI, Chen J, Deshmukh G, Estrada AA, Fuji RN, Gibbons P, Gustafson A, Harris SF, Imperio J, Liu W, Liu X, Liu Y, Lyssikatos JP, Ma C, Yin J, Lewcock JW, Siu M. Patel S, et al. Among authors: estrada aa. J Med Chem. 2017 Oct 12;60(19):8083-8102. doi: 10.1021/acs.jmedchem.7b00843. Epub 2017 Sep 20. J Med Chem. 2017. PMID: 28929759
33 results