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Quantitative pharmacokinetic/pharmacodynamic analyses suggest that the 129/SVE mouse is a suitable preclinical pharmacology model for identifying small-molecule γ-secretase inhibitors.
Lu Y, Zhang L, Nolan CE, Becker SL, Atchison K, Robshaw AE, Pustilnik LR, Osgood SM, Miller EH, Stepan AF, Subramanyam C, Efremov I, Hallgren AJ, Riddell D. Lu Y, et al. J Pharmacol Exp Ther. 2011 Dec;339(3):922-34. doi: 10.1124/jpet.111.186791. Epub 2011 Sep 19. J Pharmacol Exp Ther. 2011. PMID: 21930801
Cerebrospinal fluid amyloid-β (Aβ) as an effect biomarker for brain Aβ lowering verified by quantitative preclinical analyses.
Lu Y, Riddell D, Hajos-Korcsok E, Bales K, Wood KM, Nolan CE, Robshaw AE, Zhang L, Leung L, Becker SL, Tseng E, Barricklow J, Miller EH, Osgood S, O'Neill BT, Brodney MA, Johnson DS, Pettersson M. Lu Y, et al. J Pharmacol Exp Ther. 2012 Aug;342(2):366-75. doi: 10.1124/jpet.112.192625. Epub 2012 May 4. J Pharmacol Exp Ther. 2012. PMID: 22562771 Free PMC article.
Metabolism-directed design of oxetane-containing arylsulfonamide derivatives as γ-secretase inhibitors.
Stepan AF, Karki K, McDonald WS, Dorff PH, Dutra JK, Dirico KJ, Won A, Subramanyam C, Efremov IV, O'Donnell CJ, Nolan CE, Becker SL, Pustilnik LR, Sneed B, Sun H, Lu Y, Robshaw AE, Riddell D, O'Sullivan TJ, Sibley E, Capetta S, Atchison K, Hallgren AJ, Miller E, Wood A, Obach RS. Stepan AF, et al. Among authors: lu y. J Med Chem. 2011 Nov 24;54(22):7772-83. doi: 10.1021/jm200893p. Epub 2011 Oct 26. J Med Chem. 2011. PMID: 21995460
Application of the bicyclo[1.1.1]pentane motif as a nonclassical phenyl ring bioisostere in the design of a potent and orally active γ-secretase inhibitor.
Stepan AF, Subramanyam C, Efremov IV, Dutra JK, O'Sullivan TJ, DiRico KJ, McDonald WS, Won A, Dorff PH, Nolan CE, Becker SL, Pustilnik LR, Riddell DR, Kauffman GW, Kormos BL, Zhang L, Lu Y, Capetta SH, Green ME, Karki K, Sibley E, Atchison KP, Hallgren AJ, Oborski CE, Robshaw AE, Sneed B, O'Donnell CJ. Stepan AF, et al. Among authors: lu y. J Med Chem. 2012 Apr 12;55(7):3414-24. doi: 10.1021/jm300094u. Epub 2012 Mar 29. J Med Chem. 2012. PMID: 22420884
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