Novel nicotinamide analog as inhibitor of nicotinamide N-methyltransferase期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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Novel nicotinamide analog as inhibitor of nicotinamide N-methyltransferase

Authors:	Sven Ruf Mahanandeesha Siddappa Hallur Nisha K Anchan Indu N Swamy Karthikai Raj Murugesan Sayantani Sarkar Lokesh Kananti Narasimhulu VP Rama Kishore Putta Shama Shaik Devaraj Venkatapura Chandrasekar Vishal Subhash Mane Sanjay Venkatachalapathi Kadnur Juluri Suresh Ravi Kanth Bhamidipati Manvi Singh Raghunadha Reddy Burri Rajendra Kristam Herman Schreuder Sridharan Rajagopal

Institution:	1. Integrated Drug Discovery, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany;2. Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India;3. Department of Discovery Biology, Jubilant Biosys Ltd, Bangalore 560022, India;4. Department of Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore 560022, India;5. Department of Structural Biology, Jubilant Biosys Ltd, Bangalore 560022, India;6. Department of Computational Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India;g. R&D Drug Metabolism & Pharmacokinetics, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany;h. Biologics Research, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany;i. R&D Diabetes, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany;j. Institute of Experimental Pharmacology, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany

Abstract:	Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by ～80% at 2?h when dosed in mice orally at 50?mg/kg.

Keywords:	Nicotinamide N-methyltransferase (NNMT) Ncotinamide Methyl-nicotinamide (MNA) Obesity Diabetes
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