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Soluble γ-secretase modulators selectively inhibit the production of the 42-amino acid amyloid β peptide variant and augment the production of multiple carboxy-truncated amyloid β species.
Wagner SL, Zhang C, Cheng S, Nguyen P, Zhang X, Rynearson KD, Wang R, Li Y, Sisodia SS, Mobley WC, Tanzi RE. Wagner SL, et al. Among authors: rynearson kd. Biochemistry. 2014 Feb 4;53(4):702-13. doi: 10.1021/bi401537v. Epub 2014 Jan 22. Biochemistry. 2014. PMID: 24401146 Free PMC article.
Design and synthesis of aminothiazole modulators of the gamma-secretase enzyme.
Rynearson KD, Buckle RN, Barnes KD, Herr RJ, Mayhew NJ, Paquette WD, Sakwa SA, Nguyen PD, Johnson G, Tanzi RE, Wagner SL. Rynearson KD, et al. Bioorg Med Chem Lett. 2016 Aug 15;26(16):3928-37. doi: 10.1016/j.bmcl.2016.07.011. Epub 2016 Jul 6. Bioorg Med Chem Lett. 2016. PMID: 27426299
Pharmacological and Toxicological Properties of the Potent Oral γ-Secretase Modulator BPN-15606.
Wagner SL, Rynearson KD, Duddy SK, Zhang C, Nguyen PD, Becker A, Vo U, Masliah D, Monte L, Klee JB, Echmalian CM, Xia W, Quinti L, Johnson G, Lin JH, Kim DY, Mobley WC, Rissman RA, Tanzi RE. Wagner SL, et al. Among authors: rynearson kd. J Pharmacol Exp Ther. 2017 Jul;362(1):31-44. doi: 10.1124/jpet.117.240861. Epub 2017 Apr 17. J Pharmacol Exp Ther. 2017. PMID: 28416568 Free PMC article.
Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-β in iPSC-Derived Alzheimer's Disease Neurons.
van der Kant R, Langness VF, Herrera CM, Williams DA, Fong LK, Leestemaker Y, Steenvoorden E, Rynearson KD, Brouwers JF, Helms JB, Ovaa H, Giera M, Wagner SL, Bang AG, Goldstein LSB. van der Kant R, et al. Among authors: rynearson kd. Cell Stem Cell. 2019 Mar 7;24(3):363-375.e9. doi: 10.1016/j.stem.2018.12.013. Epub 2019 Jan 24. Cell Stem Cell. 2019. PMID: 30686764 Free PMC article.
Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators.
Rynearson KD, Buckle RN, Herr RJ, Mayhew NJ, Chen X, Paquette WD, Sakwa SA, Yang J, Barnes KD, Nguyen P, Mobley WC, Johnson G, Lin JH, Tanzi RE, Wagner SL. Rynearson KD, et al. Bioorg Med Chem. 2020 Nov 15;28(22):115734. doi: 10.1016/j.bmc.2020.115734. Epub 2020 Sep 1. Bioorg Med Chem. 2020. PMID: 33007551 Free PMC article.
Preclinical validation of a potent γ-secretase modulator for Alzheimer's disease prevention.
Rynearson KD, Ponnusamy M, Prikhodko O, Xie Y, Zhang C, Nguyen P, Hug B, Sawa M, Becker A, Spencer B, Florio J, Mante M, Salehi B, Arias C, Galasko D, Head BP, Johnson G, Lin JH, Duddy SK, Rissman RA, Mobley WC, Thinakaran G, Tanzi RE, Wagner SL. Rynearson KD, et al. J Exp Med. 2021 Apr 5;218(4):e20202560. doi: 10.1084/jem.20202560. J Exp Med. 2021. PMID: 33651103 Free PMC article.
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