Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Regular Articles
Discovery of DS68702229 as a Potent, Orally Available NAMPT (Nicotinamide Phosphoribosyltransferase) Activator
Mayuko Akiu , Takashi Tsuji, Kouki Iida, Yoshitaka Sogawa, Koji Terayama, Mika Yokoyama, Jun Tanaka, Daigo Asano, Tomohiro Honda, Ken Sakurai, Anthony B. Pinkerton, Tsuyoshi Nakamura
Author information
Keywords: anti-obesity, nicotinamide phosphoribosyltransferase activator, benzoxazole, nicotinamide adenine dinucleotide (NAD+), body weight reduction
JOURNAL FREE ACCESS FULL-TEXT HTML

2021 Volume 69 Issue 11 Pages 1110-1122

Details
Full-text HTML Download PDF (1171K)
Download citation RIS

(compatible with EndNote, Reference Manager, ProCite, RefWorks)

BIB TEX

(compatible with BibDesk, LaTeX)

Text
How to download citation
Contact us
Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step of the nicotinamide adenine dinucleotide (NAD+) salvage pathway. Because NAD+ plays a pivotal role in energy metabolism and boosting NAD+ has positive effects on metabolic regulation, activation of NAMPT is an attractive therapeutic approach for the treatment of various diseases, including type 2 diabetes and obesity. Herein we report the discovery of 1-(2-phenyl-1,3-benzoxazol-6-yl)-3-(pyridin-4-ylmethyl)urea 12c (DS68702229), which was identified as a potent NAMPT activator. Compound 12c activated NAMPT, increased cellular NAD+ levels, and exhibited an excellent pharmacokinetic profile in mice after oral administration. Oral administration of compound 12c to high-fat diet-induced obese mice decreased body weight. These observations indicate that compound 12c is a promising anti-obesity drug candidate.

Fullsize Image
Content from these authors
© 2021 The Pharmaceutical Society of Japan
Previous article Next article
Favorites & Alerts

Recently viewed articles
Share this page
feedback
 Top