|
|||||
|
|
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 V.P. 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 |
| Affiliation: | 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 |
| 本文献已被 ScienceDirect 等数据库收录！ | |