Discovery of MK-5046, a Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity

Iyassu K Sebhat; Christopher Franklin; Michael M-C Lo; David Chen; James P Jewell; Randy Miller; Jianmei Pang; Oksana Palyha; Yanqing Kan; Theresa M Kelly; Xiao-Ming Guan; Donald J Marsh; Jennifer A Kosinski; Joseph M Metzger; Kathryn Lyons; Jasminka Dragovic; Peter R Guzzo; Alan J Henderson; Marc L Reitman; Ravi P Nargund; Matthew J Wyvratt; Linus S Lin

doi:10.1021/ml100196d

Discovery of MK-5046, a Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity

ACS Med Chem Lett. 2010 Oct 18;2(1):43-7. doi: 10.1021/ml100196d. eCollection 2011 Jan 13.

Authors

Iyassu K Sebhat¹, Christopher Franklin¹, Michael M-C Lo¹, David Chen¹, James P Jewell¹, Randy Miller², Jianmei Pang², Oksana Palyha³, Yanqing Kan³, Theresa M Kelly³, Xiao-Ming Guan³, Donald J Marsh³, Jennifer A Kosinski³, Joseph M Metzger⁴, Kathryn Lyons², Jasminka Dragovic², Peter R Guzzo⁵, Alan J Henderson⁵, Marc L Reitman³, Ravi P Nargund¹, Matthew J Wyvratt¹, Linus S Lin¹

Affiliations

¹ Departments of Medicinal Chemistry.
² Drug Metabolism.
³ Metabolic Diseases (Obesity).
⁴ Pharmacology.
⁵ AMRI, 26 Corporate Circle, Albany, New York 12212, United States.

Abstract

We report the development and characterization of compound 22 (MK-5046), a potent, selective small molecule agonist of BRS-3 (bombesin receptor subtype-3). In pharmacological testing using diet-induced obese mice, compound 22 caused mechanism-based, dose-dependent reductions in food intake and body weight.

Keywords: MK-5046; bombesin receptor subtype-3 agonist; obesity.