Therapeutic safety implications of SARM1 active site inhibitors: subinhibitory concentrations cause neurodegeneration.

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Title: Therapeutic safety implications of SARM1 active site inhibitors: subinhibitory concentrations cause neurodegeneration.
Authors: Leahey RR; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA., Weber M; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA., Cho CH; Department of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, CA, 94080, USA., Hur SK; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA., Cramer A; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA., Manzanares K; Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA., Babin B; Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA., Boenig G; Department of Structural Biology, Genentech, Inc., South San Francisco, CA, 94080, USA., Kring T; Department of Pharmaceutics, Genentech, Inc., South San Francisco, CA, 94080, USA., Liu L; Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., South San Francisco, CA, 94080, USA., Cui Y; Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., South San Francisco, CA, 94080, USA., Ganti A; Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., South San Francisco, CA, 94080, USA., Evans JP; Arctoris Ltd, 120E Olympic Avenue, OX14 4SA, Abingdon, United Kingdom., Nespi M; Department of Pharmaceutics, Genentech, Inc., South San Francisco, CA, 94080, USA., Ly J; Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., South San Francisco, CA, 94080, USA., Nugent AA; Department of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, CA, 94080, USA., Green SA; Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, 94080, USA., Chan BK; Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, 94080, USA., Hoogenraad CC; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA., Delwig A; Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA. delwig.anton@gene.com., Hinz FI; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA. hinz.flora@gene.com.
Source: Npj drug discovery [NPJ Drug Discov] 2025 Aug 25; Vol. 2 (1). Date of Electronic Publication: 2025 Aug 25.
Publication Type: Journal Article
Journal Info: Publisher: Nature Portfolio Country of Publication: England NLM ID: 9918993695206676 Publication Model: Electronic Cited Medium: Internet ISSN: 3005-1452 (Electronic) Linking ISSN: 30051452 NLM ISO Abbreviation: NPJ Drug Discov Subsets: PubMed not MEDLINE
Database: MEDLINE Ultimate
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  Data: <searchLink fieldCode="AU" term="%22Leahey+RR%22">Leahey RR</searchLink>; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Weber+M%22">Weber M</searchLink>; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Cho+CH%22">Cho CH</searchLink>; Department of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Hur+SK%22">Hur SK</searchLink>; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Cramer+A%22">Cramer A</searchLink>; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Manzanares+K%22">Manzanares K</searchLink>; Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Babin+B%22">Babin B</searchLink>; Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Boenig+G%22">Boenig G</searchLink>; Department of Structural Biology, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Kring+T%22">Kring T</searchLink>; Department of Pharmaceutics, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Liu+L%22">Liu L</searchLink>; Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Cui+Y%22">Cui Y</searchLink>; Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Ganti+A%22">Ganti A</searchLink>; Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Evans+JP%22">Evans JP</searchLink>; Arctoris Ltd, 120E Olympic Avenue, OX14 4SA, Abingdon, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Nespi+M%22">Nespi M</searchLink>; Department of Pharmaceutics, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Ly+J%22">Ly J</searchLink>; Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Nugent+AA%22">Nugent AA</searchLink>; Department of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Green+SA%22">Green SA</searchLink>; Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Chan+BK%22">Chan BK</searchLink>; Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Hoogenraad+CC%22">Hoogenraad CC</searchLink>; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA.<br /><searchLink fieldCode="AU" term="%22Delwig+A%22">Delwig A</searchLink>; Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, 94080, USA. delwig.anton@gene.com.<br /><searchLink fieldCode="AU" term="%22Hinz+FI%22">Hinz FI</searchLink>; Department of Neuroscience, Genentech, Inc., South San Francisco, CA, 94080, USA. hinz.flora@gene.com.
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