Chronic Collection of Cerebrospinal Fluid from Rhesus Macaques ( Macaca mulatta ) with Cisterna Magna Ports: Update on Refinements.

Autor: Gilberto DB; Safety Assessment Laboratory Animal Resources, Company, Kenilworth, New Jersey., Michener MS; Safety Assessment Laboratory Animal Resources, Company, Kenilworth, New Jersey., Smith BE; Safety Assessment Laboratory Animal Resources, Company, Kenilworth, New Jersey., Szczerba PJ; Clinical Pathology, Company, Kenilworth, New Jersey., Holahan MA; Translational Imaging Biomarkers, Merck, Company, Kenilworth, New Jersey., Gray TL; Safety Assessment Laboratory Animal Resources, Company, Kenilworth, New Jersey., Motzel SL; Safety Assessment Laboratory Animal Resources, Company, Kenilworth, New Jersey.

Publikováno v: Comparative medicine [Comp Med] 2022 Feb 01; Vol. 72 (1), pp. 45-49. Date of Electronic Publication: 2021 Dec 13.

Extending a Systems Model of the APP Pathway: Separation of β - and γ -Secretase Sequential Cleavage Steps of APP.

Autor: van Maanen EMT; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.)., van Steeg TJ; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.)., Ahsman MJ; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.)., Michener MS; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.)., Savage MJ; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.)., Kennedy ME; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.)., Kleijn HJ; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.)., Stone J; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.)., Danhof M; Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (E.M.T.v.M., M.D.); Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands (E.M.T.v.M., T.J.v.S., M.J.A.); and Merck & Company, Inc., Kenilworth, New Jersey (M.S.M., M.J.S., M.E.K., H.J.K., J.S.) m.danhof@lacdr.leidenuniv.nl.

Publikováno v: The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2018 Jun; Vol. 365 (3), pp. 507-518. Date of Electronic Publication: 2018 Mar 21.

Structure-Based Design of an Iminoheterocyclic β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central Aβ in Nonhuman Primates.

Autor: Mandal M; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Wu Y; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Misiaszek J; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Li G; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Buevich A; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Caldwell JP; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Liu X; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Mazzola RD; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Orth P; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Strickland C; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Voigt J; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Wang H; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Zhu Z; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Chen X; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Grzelak M; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Hyde LA; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Kuvelkar R; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Leach PT; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Terracina G; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Zhang L; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Zhang Q; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Michener MS; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Smith B; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Cox K; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Grotz D; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Favreau L; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Mitra K; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Kazakevich I; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., McKittrick BA; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Greenlee W; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Kennedy ME; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Parker EM; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Cumming JN; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States., Stamford AW; Department of Global Chemistry, ‡Department of Neuroscience, §Department of Safety Assessment and Laboratory Animal Research, ∥Department of Discovery Pharmaceutical Sciences, and ⊥Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2016 Apr 14; Vol. 59 (7), pp. 3231-48. Date of Electronic Publication: 2016 Mar 22.

Discovery of novel triazolobenzazepinones as γ-secretase modulators with central Aβ42 lowering in rodents and rhesus monkeys.

Autor: Fischer C; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: Christian_fischer@merck.com., Zultanski SL; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Zhou H; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Methot JL; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Shah S; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Hayashi I; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Hughes BL; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Moxham CM; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Bays NW; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Smotrov N; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Hill AD; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Pan BS; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Wu Z; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Moy LY; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Tanga F; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Kenific C; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Cruz JC; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Walker D; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Bouthillette M; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Nikov GN; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Deshmukh SV; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Jeliazkova-Mecheva VV; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Diaz D; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Michener MS; Merck Research Laboratories West Point, 770 Sumneytown Pike, West Point, PA 19486, USA., Cook JJ; Merck Research Laboratories West Point, 770 Sumneytown Pike, West Point, PA 19486, USA., Munoz B; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA., Shearman MS; Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.

Publikováno v: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Sep 01; Vol. 25 (17), pp. 3488-94. Date of Electronic Publication: 2015 Jul 09.

CNS amyloid-β, soluble APP-α and -β kinetics during BACE inhibition.

Autor: Dobrowolska JA; Departments of Neurology and., Michener MS; Safety and Laboratory Animal Resources., Wu G; Molecular Biomarkers., Patterson BW; Medicine, Washington University School of Medicine, St. Louis, Missouri 63110 and., Chott R; Medicine, Washington University School of Medicine, St. Louis, Missouri 63110 and., Ovod V; Departments of Neurology and., Pyatkivskyy Y; Departments of Neurology and., Wildsmith KR; Departments of Neurology and., Kasten T; Departments of Neurology and., Mathers P; Safety and Laboratory Animal Resources., Dancho M; Safety and Laboratory Animal Resources., Lennox C; Safety and Laboratory Animal Resources., Smith BE; Safety and Laboratory Animal Resources., Gilberto D; Safety and Laboratory Animal Resources., McLoughlin D; Preclinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486 and Kenilworth, New Jersey 07033., Holder DJ; Early Development Statistics, and., Stamford AW; Medicinal Chemistry., Yarasheski KE; Medicine, Washington University School of Medicine, St. Louis, Missouri 63110 and., Kennedy ME; Neuroscience., Savage MJ; Molecular Biomarkers., Bateman RJ; Departments of Neurology and batemanr@wustl.edu.

Publikováno v: The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2014 Jun 11; Vol. 34 (24), pp. 8336-46.