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Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor.
Henderson JL, Kormos BL, Hayward MM, Coffman KJ, Jasti J, Kurumbail RG, Wager TT, Verhoest PR, Noell GS, Chen Y, Needle E, Berger Z, Steyn SJ, Houle C, Hirst WD, Galatsis P. Henderson JL, et al. Among authors: chen y. J Med Chem. 2015 Jan 8;58(1):419-32. doi: 10.1021/jm5014055. Epub 2014 Nov 17. J Med Chem. 2015. PMID: 25353650
Wild-type GBA1 increases the α-synuclein tetramer-monomer ratio, reduces lipid-rich aggregates, and attenuates motor and cognitive deficits in mice.
Glajch KE, Moors TE, Chen Y, Bechade PA, Nam AY, Rajsombath MM, McCaffery TD, Dettmer U, Weihofen A, Hirst WD, Selkoe DJ, Nuber S. Glajch KE, et al. Among authors: chen y. Proc Natl Acad Sci U S A. 2021 Aug 3;118(31):e2103425118. doi: 10.1073/pnas.2103425118. Proc Natl Acad Sci U S A. 2021. PMID: 34326260 Free PMC article.
The Parkinson's disease-associated gene ITPKB protects against α-synuclein aggregation by regulating ER-to-mitochondria calcium release.
Apicco DJ, Shlevkov E, Nezich CL, Tran DT, Guilmette E, Nicholatos JW, Bantle CM, Chen Y, Glajch KE, Abraham NA, Dang LT, Kaynor GC, Tsai EA, Nguyen KH, Groot J, Liu Y, Weihofen A, Hurt JA, Runz H, Hirst WD. Apicco DJ, et al. Among authors: chen y. Proc Natl Acad Sci U S A. 2021 Jan 5;118(1):e2006476118. doi: 10.1073/pnas.2006476118. Proc Natl Acad Sci U S A. 2021. PMID: 33443159 Free PMC article.
Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein.
Patterson JR, Hirst WD, Howe JW, Russell CP, Cole-Strauss A, Kemp CJ, Duffy MF, Lamp J, Umstead A, Kubik M, Stoll AC, Vega IE, Steece-Collier K, Chen Y, Campbell AC, Nezich CL, Glajch KE, Sortwell CE. Patterson JR, et al. Among authors: chen y. NPJ Parkinsons Dis. 2022 May 24;8(1):61. doi: 10.1038/s41531-022-00322-x. NPJ Parkinsons Dis. 2022. PMID: 35610264 Free PMC article.
Decreased glucocerebrosidase activity and substrate accumulation of glycosphingolipids in a novel GBA1 D409V knock-in mouse model.
Polinski NK, Martinez TN, Gorodinsky A, Gareus R, Sasner M, Herberth M, Switzer R, Ahmad SO, Cosden M, Kandebo M, Drolet RE, Buckett PD, Shan W, Chen Y, Pellegrino LJ, Ellsworth GD, Dungan LB, Hirst WD, Clark SW, Dave KD. Polinski NK, et al. Among authors: chen y. PLoS One. 2021 Jun 9;16(6):e0252325. doi: 10.1371/journal.pone.0252325. eCollection 2021. PLoS One. 2021. PMID: 34106956 Free PMC article.
Discovery and in vivo evaluation of (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and related PI3Kδ inhibitors for inflammation and autoimmune disease.
Cushing TD, Hao X, Shin Y, Andrews K, Brown M, Cardozo M, Chen Y, Duquette J, Fisher B, Gonzalez-Lopez de Turiso F, He X, Henne KR, Hu YL, Hungate R, Johnson MG, Kelly RC, Lucas B, McCarter JD, McGee LR, Medina JC, San Miguel T, Mohn D, Pattaropong V, Pettus LH, Reichelt A, Rzasa RM, Seganish J, Tasker AS, Wahl RC, Wannberg S, Whittington DA, Whoriskey J, Yu G, Zalameda L, Zhang D, Metz DP. Cushing TD, et al. Among authors: chen y. J Med Chem. 2015 Jan 8;58(1):480-511. doi: 10.1021/jm501624r. Epub 2014 Dec 3. J Med Chem. 2015. PMID: 25469863
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