Literature DB >> 24900253

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

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.   

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.

Entities:  

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

Year:  2010        PMID： 24900253      PMCID： PMC4018145          DOI： 10.1021/ml100196d

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  13 in total

1.  Design of selective peptidomimetic agonists for the human orphan receptor BRS-3.

Authors:  Dirk Weber; Claudia Berger; Peter Eickelmann; Jochen Antel; Horst Kessler
Journal:  J Med Chem       Date:  2003-05-08       Impact factor: 7.446

Review 2.  Two distinct receptor subtypes for mammalian bombesin-like peptides.

Authors:  J Battey; E Wada
Journal:  Trends Neurosci       Date:  1991-12       Impact factor: 13.837

3.  Synthesis and SAR of heterocyclic carboxylic acid isosteres based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity.

Authors:  Mark Hadden; Allan Goodman; Cheng Guo; Peter R Guzzo; Alan J Henderson; Kevin Pattamana; Megan Ruenz; Bruce J Sargent; Brian Swenson; Larry Yet; Jian Liu; Shuwen He; Iyassu K Sebhat; Linus S Lin; Constantin Tamvakopoulos; Qianping Peng; Yanqing Kan; Oksana Palyha; Theresa M Kelly; Xiao-Ming Guan; Joseph M Metzger; Marc L Reitman; Ravi P Nargund
Journal:  Bioorg Med Chem Lett       Date:  2010-03-12       Impact factor: 2.823

4.  Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity.

Authors:  Jian Liu; Shuwen He; Tianying Jian; Peter H Dobbelaar; Iyassu K Sebhat; Linus S Lin; Allan Goodman; Cheng Guo; Peter R Guzzo; Mark Hadden; Alan J Henderson; Kevin Pattamana; Megan Ruenz; Bruce J Sargent; Brian Swenson; Larry Yet; Constantin Tamvakopoulos; Qianping Peng; Jie Pan; Yanqing Kan; Oksana Palyha; Theresa M Kelly; Xiao-Ming Guan; Andrew D Howard; Donald J Marsh; Joseph M Metzger; Marc L Reitman; Matthew J Wyvratt; Ravi P Nargund
Journal:  Bioorg Med Chem Lett       Date:  2010-02-21       Impact factor: 2.823

5.  Synthesis of 7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-1-ylamine and its analogs as bombesin receptor subtype-3 agonists.

Authors:  Cheng Guo; Peter R Guzzo; Mark Hadden; Bruce J Sargent; Larry Yet; Yanqing Kan; Oksana Palyha; Theresa M Kelly; Xiaoming Guan; Kim Rosko; Karen Gagen; Joseph M Metzger; Jasminka Dragovic; Kathryn Lyons; Linus S Lin; Ravi P Nargund
Journal:  Bioorg Med Chem Lett       Date:  2010-03-17       Impact factor: 2.823

6.  Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists.

Authors:  Shuwen He; Peter H Dobbelaar; Jian Liu; Tianying Jian; Iyassu K Sebhat; Linus S Lin; Allan Goodman; Cheng Guo; Peter R Guzzo; Mark Hadden; Alan J Henderson; Megan Ruenz; Bruce J Sargent; Larry Yet; Theresa M Kelly; Oksana Palyha; Yanqing Kan; Jie Pan; Howard Chen; Donald J Marsh; Lauren P Shearman; Alison M Strack; Joseph M Metzger; Scott D Feighner; Carina Tan; Andrew D Howard; Constantin Tamvakopoulos; Qianping Peng; Xiao-Ming Guan; Marc L Reitman; Arthur A Patchett; Matthew J Wyvratt; Ravi P Nargund
Journal:  Bioorg Med Chem Lett       Date:  2010-02-04       Impact factor: 2.823

7.  Discovery of small molecule agonists for the bombesin receptor subtype 3 (BRS-3) based on an omeprazole lead.

Authors:  David L Carlton; Lissa J Collin-Smith; Alejandro J Daniels; David N Deaton; Aaron S Goetz; Christopher P Laudeman; Thomas R Littleton; David L Musso; Ronda J Ott Morgan; Jerzy R Szewczyk; Cunyu Zhang
Journal:  Bioorg Med Chem Lett       Date:  2008-09-11       Impact factor: 2.823

8.  Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity.

Authors:  H Ohki-Hamazaki; K Watase; K Yamamoto; H Ogura; M Yamano; K Yamada; H Maeno; J Imaki; S Kikuyama; E Wada; K Wada
Journal:  Nature       Date:  1997-11-13       Impact factor: 49.962

9.  Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity.

Authors:  Xiao-Ming Guan; Howard Chen; Peter H Dobbelaar; Yan Dong; Tung M Fong; Karen Gagen; Judith Gorski; Shuwen He; Andrew D Howard; Tianying Jian; Michael Jiang; Yanqing Kan; Theresa M Kelly; Jennifer Kosinski; Linus S Lin; Jian Liu; Donald J Marsh; Joseph M Metzger; Randy Miller; Ravi P Nargund; Oksana Palyha; Lauren Shearman; Zhu Shen; Ralph Stearns; Alison M Strack; Sloan Stribling; Yui Sing Tang; Sheng-Ping Wang; Amanda White; Hong Yu; Marc L Reitman
Journal:  Cell Metab       Date:  2010-01-21       Impact factor: 27.287

Review 10.  International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states.

Authors:  R T Jensen; J F Battey; E R Spindel; R V Benya
Journal:  Pharmacol Rev       Date:  2007-11-30       Impact factor: 25.468
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  20 in total

1.  Pharmacokinetics and pharmacodynamics of MK-5046, a bombesin receptor subtype-3 (BRS-3) agonist, in healthy patients.

Authors:  Marc L Reitman; Victor Dishy; Allison Moreau; William S Denney; Chengcheng Liu; Walter K Kraft; Alex V Mejia; Mark A Matson; S Aubrey Stoch; John A Wagner; Eseng Lai
Journal:  J Clin Pharmacol       Date:  2011-12-12       Impact factor: 3.126

2.  Regulation of body temperature and brown adipose tissue thermogenesis by bombesin receptor subtype-3.

Authors:  Dalya M Lateef; Gustavo Abreu-Vieira; Cuiying Xiao; Marc L Reitman
Journal:  Am J Physiol Endocrinol Metab       Date:  2014-01-22       Impact factor: 4.310

Review 3.  Insights into bombesin receptors and ligands: Highlighting recent advances.

Authors:  Irene Ramos-Álvarez; Paola Moreno; Samuel A Mantey; Taichi Nakamura; Bernardo Nuche-Berenguer; Terry W Moody; David H Coy; Robert T Jensen
Journal:  Peptides       Date:  2015-05-11       Impact factor: 3.750

Review 4.  Bombesin receptor subtype 3 as a potential target for obesity and diabetes.

Authors:  Nieves González; Paola Moreno; Robert T Jensen
Journal:  Expert Opin Ther Targets       Date:  2015-06-12       Impact factor: 6.902

5.  Development and Characterization of a Novel, High-Affinity, Specific, Radiolabeled Ligand for BRS-3 Receptors.

Authors:  Irene Ramos-Alvarez; Lingaku Lee; Samuel A Mantey; Robert T Jensen
Journal:  J Pharmacol Exp Ther       Date:  2019-04-10       Impact factor: 4.030

6.  Discovery of benzodiazepine sulfonamide-based bombesin receptor subtype 3 agonists and their unusual chirality.

Authors:  Ping Liu; Thomas J Lanza; Marc Chioda; Carrie Jones; Harry R Chobanian; Yan Guo; Linda Chang; Theresa M Kelly; Yanqing Kan; Oksana Palyha; Xiao-Ming Guan; Donald J Marsh; Joseph M Metzger; Katie Ramsay; Sheng-Ping Wang; Alison M Strack; Randy Miller; Jianmei Pang; Kathy Lyons; Jasminka Dragovic; Jian G Ning; Wes A Schafer; Christopher J Welch; Xiaoyi Gong; Ying-Duo Gao; Viktor Hornak; Richard G Ball; Nancy Tsou; Marc L Reitman; Matthew J Wyvratt; Ravi P Nargund; Linus S Lin
Journal:  ACS Med Chem Lett       Date:  2011-10-03       Impact factor: 4.345

7.  Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity.

Authors:  Harry R Chobanian; Yan Guo; Ping Liu; Marc Chioda; Thomas J Lanza; Linda Chang; Theresa M Kelly; Yanqing Kan; Oksana Palyha; Xiao-Ming Guan; Donald J Marsh; Joseph M Metzger; Judith N Gorski; Kate Raustad; Sheng-Ping Wang; Alison M Strack; Randy Miller; Jianmei Pang; Maria Madeira; Kathy Lyons; Jasminka Dragovic; Marc L Reitman; Ravi P Nargund; Linus S Lin
Journal:  ACS Med Chem Lett       Date:  2012-01-21       Impact factor: 4.345

8.  Molecular basis for high affinity and selectivity of peptide antagonist, Bantag-1, for the orphan BB3 receptor.

Authors:  Taichi Nakamura; Irene Ramos-Álvarez; Tatiana Iordanskaia; Paola Moreno; Samuel A Mantey; R T Jensen
Journal:  Biochem Pharmacol       Date:  2016-06-23       Impact factor: 5.858

9.  Comparative pharmacology of bombesin receptor subtype-3, nonpeptide agonist MK-5046, a universal peptide agonist, and peptide antagonist Bantag-1 for human bombesin receptors.

Authors:  Paola Moreno; Samuel A Mantey; Bernardo Nuche-Berenguer; Marc L Reitman; Nieves González; David H Coy; Robert T Jensen
Journal:  J Pharmacol Exp Ther       Date:  2013-07-26       Impact factor: 4.030

10.  Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism.

Authors:  Dalya M Lateef; Cuiying Xiao; Robert J Brychta; André Diedrich; Jurgen Schnermann; Marc L Reitman
Journal:  Am J Physiol Heart Circ Physiol       Date:  2016-01-22       Impact factor: 4.733
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