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Discovery of novel cyclopentane carboxylic acids as potent and selective inhibitors of Na V 1.7.

Autor: Sun S; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada. Electronic address: ssun@xenon-pharma.com., Chowdhury S; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Hemeon I; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Hasan A; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Wilson MS; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Bergeron P; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Jia Q; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Zenova AY; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Grimwood ME; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Gong W; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Decker SM; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Bichler P; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Andrez JC; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Focken T; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Ngyuen T; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Zhu J; Chempartner, Building No. 5, 998 Halei Rd., Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai, PR China., White AD; Chempartner, Building No. 5, 998 Halei Rd., Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai, PR China., Bankar G; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Howard S; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Chang E; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Khakh K; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Lin S; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Dean R; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Johnson JP Jr; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Chang JH; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Hackos DH; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., McKerrall SJ; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Sellers B; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Ortwine DF; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Cohen CJ; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada., Safina BS; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Sutherlin DP; Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA., Dehnhardt CM; Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada.

Publikováno v: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2024 Nov 21, pp. 130033. Date of Electronic Publication: 2024 Nov 21.

Discovery of Acyl-sulfonamide Na v 1.7 Inhibitors GDC-0276 and GDC-0310.

Autor: Safina BS; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., McKerrall SJ; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Sun S; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Chen CA; Chempartner, Building No. 5, 998 Halei Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, P.R. China., Chowdhury S; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Jia Q; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Li J; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Zenova AY; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Andrez JC; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Bankar G; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Bergeron P; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Chang JH; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Chang E; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Chen J; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Dean R; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Decker SM; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., DiPasquale A; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Focken T; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Hemeon I; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Khakh K; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Kim A; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Kwan R; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Lindgren A; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Lin S; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Maher J; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Mezeyova J; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Misner D; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Nelkenbrecher K; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Pang J; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Reese R; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Shields SD; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Sojo L; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Sheng T; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Verschoof H; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Waldbrook M; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Wilson MS; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Xie Z; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Young C; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Zabka TS; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Hackos DH; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Ortwine DF; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., White AD; Chempartner, Building No. 5, 998 Halei Road, Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, P.R. China., Johnson JP Jr; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Robinette CL; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Dehnhardt CM; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Cohen CJ; Xenon Pharmaceuticals, Inc., 200-3650 Gilmore Way, Burnaby, British Columbia V5G 4W8, Canada., Sutherlin DP; Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2021 Mar 25; Vol. 64 (6), pp. 2953-2966. Date of Electronic Publication: 2021 Mar 08.

Structure- and Ligand-Based Discovery of Chromane Arylsulfonamide Na v 1.7 Inhibitors for the Treatment of Chronic Pain.

Autor: McKerrall SJ; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Nguyen T; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Lai KW; WuXi AppTec Co., Ltd. , 288 Fute Zhong Road , Waigaoqiao Free Trade Zone, Shanghai 200131 , People's Republic of China., Bergeron P; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Deng L; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., DiPasquale A; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Chang JH; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Chen J; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Chernov-Rogan T; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Hackos DH; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Maher J; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Ortwine DF; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Pang J; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Payandeh J; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Proctor WR; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Shields SD; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Vogt J; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Ji P; WuXi AppTec Co., Ltd. , 288 Fute Zhong Road , Waigaoqiao Free Trade Zone, Shanghai 200131 , People's Republic of China., Liu W; WuXi AppTec Co., Ltd. , 288 Fute Zhong Road , Waigaoqiao Free Trade Zone, Shanghai 200131 , People's Republic of China., Ballini E; Evotec AG , Essener Bogen 7 , 22419 Hamburg , Germany., Schumann L; Evotec AG , Essener Bogen 7 , 22419 Hamburg , Germany., Tarozzo G; Evotec AG , Essener Bogen 7 , 22419 Hamburg , Germany., Bankar G; Xenon Pharmaceuticals, Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada., Chowdhury S; Xenon Pharmaceuticals, Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada., Hasan A; Xenon Pharmaceuticals, Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada., Johnson JP Jr; Xenon Pharmaceuticals, Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada., Khakh K; Xenon Pharmaceuticals, Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada., Lin S; Xenon Pharmaceuticals, Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada., Cohen CJ; Xenon Pharmaceuticals, Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada., Dehnhardt CM; Xenon Pharmaceuticals, Inc. , 200-3650 Gilmore Way , Burnaby , British Columbia V5G 4W8 , Canada., Safina BS; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States., Sutherlin DP; Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2019 Apr 25; Vol. 62 (8), pp. 4091-4109. Date of Electronic Publication: 2019 Apr 16.

Selective Na V 1.7 Antagonists with Long Residence Time Show Improved Efficacy against Inflammatory and Neuropathic Pain.

Autor: Bankar G; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Goodchild SJ; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Howard S; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Nelkenbrecher K; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Waldbrook M; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Dourado M; Genentech, South San Francisco, CA 94080, USA., Shuart NG; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Lin S; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Young C; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Xie Z; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Khakh K; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Chang E; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Sojo LE; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Lindgren A; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Chowdhury S; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Decker S; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Grimwood M; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Andrez JC; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Dehnhardt CM; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Pang J; Genentech, South San Francisco, CA 94080, USA., Chang JH; Genentech, South San Francisco, CA 94080, USA., Safina BS; Genentech, South San Francisco, CA 94080, USA., Sutherlin DP; Genentech, South San Francisco, CA 94080, USA., Johnson JP Jr; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Hackos DH; Genentech, South San Francisco, CA 94080, USA., Robinette CL; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada., Cohen CJ; Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada. Electronic address: ccohen@xenon-pharma.com.

Publikováno v: Cell reports [Cell Rep] 2018 Sep 18; Vol. 24 (12), pp. 3133-3145.