Ontology highlight
ABSTRACT:
SUBMITTER: Policarpo RL
PROVIDER: S-EPMC7955893 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Policarpo Rocco L RL Decultot Ludovic L May Elizabeth E Kuzmič Petr P Carlson Samuel S Huang Danny D Chu Vincent V Wright Brandon A BA Dhakshinamoorthy Saravanakumar S Kannt Aimo A Rani Shilpa S Dittakavi Sreekanth S Panarese Joseph D JD Gaudet Rachelle R Shair Matthew D MD
Journal of medicinal chemistry 20191025 21
Nicotinamide <i>N</i>-methyltransferase (NNMT) is a metabolic enzyme that methylates nicotinamide (NAM) using cofactor <i>S</i>-adenosylmethionine (SAM). NNMT overexpression has been linked to diabetes, obesity, and various cancers. In this work, structure-based rational design led to the development of potent and selective alkynyl bisubstrate inhibitors of NNMT. The reported nicotinamide-SAM conjugate (named NS1) features an alkyne as a key design element that closely mimics the linear, 180° tr ...[more]