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A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models.
van Lengerich B, Zhan L, Xia D, Chan D, Joy D, Park JI, Tatarakis D, Calvert M, Hummel S, Lianoglou S, Pizzo ME, Prorok R, Thomsen E, Bartos LM, Beumers P, Capell A, Davis SS, de Weerd L, Dugas JC, Duque J, Earr T, Gadkar K, Giese T, Gill A, Gnörich J, Ha C, Kannuswamy M, Kim DJ, Kunte ST, Kunze LH, Lac D, Lechtenberg K, Leung AW, Liang CC, Lopez I, McQuade P, Modi A, Torres VO, Nguyen HN, Pesämaa I, Propson N, Reich M, Robles-Colmenares Y, Schlepckow K, Slemann L, Solanoy H, Suh JH, Thorne RG, Vieira C, Wind-Mark K, Xiong K, Zuchero YJY, Diaz D, Dennis MS, Huang F, Scearce-Levie K, Watts RJ, Haass C, Lewcock JW, Di Paolo G, Brendel M, Sanchez PE, Monroe KM. van Lengerich B, et al. Among authors: scearce levie k. Nat Neurosci. 2023 Mar;26(3):416-429. doi: 10.1038/s41593-022-01240-0. Epub 2023 Jan 12. Nat Neurosci. 2023. PMID: 36635496 Free PMC article.
Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design.
Volgraf M, Sellers BD, Jiang Y, Wu G, Ly CQ, Villemure E, Pastor RM, Yuen PW, Lu A, Luo X, Liu M, Zhang S, Sun L, Fu Y, Lupardus PJ, Wallweber HJ, Liederer BM, Deshmukh G, Plise E, Tay S, Reynen P, Herrington J, Gustafson A, Liu Y, Dirksen A, Dietz MG, Liu Y, Wang TM, Hanson JE, Hackos D, Scearce-Levie K, Schwarz JB. Volgraf M, et al. J Med Chem. 2016 Mar 24;59(6):2760-79. doi: 10.1021/acs.jmedchem.5b02010. Epub 2016 Mar 8. J Med Chem. 2016. PMID: 26919761
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
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
Dual leucine zipper kinase is required for excitotoxicity-induced neuronal degeneration.
Pozniak CD, Sengupta Ghosh A, Gogineni A, Hanson JE, Lee SH, Larson JL, Solanoy H, Bustos D, Li H, Ngu H, Jubb AM, Ayalon G, Wu J, Scearce-Levie K, Zhou Q, Weimer RM, Kirkpatrick DS, Lewcock JW. Pozniak CD, et al. J Exp Med. 2013 Nov 18;210(12):2553-67. doi: 10.1084/jem.20122832. Epub 2013 Oct 28. J Exp Med. 2013. PMID: 24166713 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
Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates.
Yu YJ, Atwal JK, Zhang Y, Tong RK, Wildsmith KR, Tan C, Bien-Ly N, Hersom M, Maloney JA, Meilandt WJ, Bumbaca D, Gadkar K, Hoyte K, Luk W, Lu Y, Ernst JA, Scearce-Levie K, Couch JA, Dennis MS, Watts RJ. Yu YJ, et al. Sci Transl Med. 2014 Nov 5;6(261):261ra154. doi: 10.1126/scitranslmed.3009835. Sci Transl Med. 2014. PMID: 25378646
80 results