Literature DB >> 30108796

Small structural changes of the imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitors produce an improved safety profile.

K Futatsugi1, K Huard1, D W Kung2, J C Pettersen3, D A Flynn3, J R Gosset1, G E Aspnes1, R J Barnes3, S Cabral2, M S Dowling2, D P Fernando2, T C Goosen2, W P Gorczyca3, D Hepworth1, M Herr2, S Lavergne2, Q Li2, M Niosi2, S T M Orr2, I D Pardo3, S M Perez4, J Purkal4, T J Schmahai3, N Shirai3, A M Shoieb3, J Zhou3, B Goodwin4.   

Abstract

Small molecule DGAT2 inhibitors have shown promise for the treatment of metabolic diseases in preclinical models. Herein, we report the first toxicological evaluation of imidazopyridine-based DGAT2 inhibitors and show that the arteriopathy associated with imidazopyridine 1 can be mitigated with small structural modifications, and is thus not mechanism related.

Entities:  

Year:  2016        PMID： 30108796      PMCID： PMC6072535          DOI： 10.1039/c6md00564k

Source DB:  PubMed          Journal:  Medchemcomm        ISSN： 2040-2503            Impact factor:   3.597


  38 in total

1.  Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

Authors:  Katherine L Gill; J Brian Houston; Aleksandra Galetin
Journal:  Drug Metab Dispos       Date:  2012-01-24       Impact factor: 3.922

Review 2.  DGAT1 inhibitors as anti-obesity and anti-diabetic agents.

Authors:  Alan M Birch; Linda K Buckett; Andrew V Turnbull
Journal:  Curr Opin Drug Discov Devel       Date:  2010-07

3.  Diacylglycerol acyltransferase 2 acts upstream of diacylglycerol acyltransferase 1 and utilizes nascent diglycerides and de novo synthesized fatty acids in HepG2 cells.

Authors:  Haja R Wurie; Linda Buckett; Victor A Zammit
Journal:  FEBS J       Date:  2012-07-31       Impact factor: 5.542

4.  The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters.

Authors:  Chi-Liang Eric Yen; Mara Monetti; Betty J Burri; Robert V Farese
Journal:  J Lipid Res       Date:  2005-04-16       Impact factor: 5.922

5.  Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members.

Authors:  S Cases; S J Stone; P Zhou; E Yen; B Tow; K D Lardizabal; T Voelker; R V Farese
Journal:  J Biol Chem       Date:  2001-07-31       Impact factor: 5.157

6.  Discovery of indolyl acrylamide derivatives as human diacylglycerol acyltransferase-2 selective inhibitors.

Authors:  Kyeong Lee; Minkyoung Kim; Boah Lee; Jail Goo; Jiyoung Kim; Ravi Naik; Jee Hee Seo; Mun Ock Kim; Youngjoo Byun; Gyu-Yong Song; Hyun Sun Lee; Yongseok Choi
Journal:  Org Biomol Chem       Date:  2012-12-17       Impact factor: 3.876

7.  Lipopenia and skin barrier abnormalities in DGAT2-deficient mice.

Authors:  Scot J Stone; Heather M Myers; Steven M Watkins; Barbara E Brown; Kenneth R Feingold; Peter M Elias; Robert V Farese
Journal:  J Biol Chem       Date:  2003-12-10       Impact factor: 5.157

8.  Identification of DGAT2 Inhibitors Using Mass Spectrometry.

Authors:  Xuelei S Song; Jiaping Zhang; Xun Chen; Oksana Palyha; Christine Chung; Lisa M Sonatore; Larissa Wilsie; Steven Stout; David G McLaren; Andrew Taggart; Jason E Imbriglio; Shirly Pinto; Margarita Garcia-Calvo; George H Addona
Journal:  J Biomol Screen       Date:  2015-09-24

Review 9.  Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis.

Authors:  Chi-Liang Eric Yen; Scot J Stone; Suneil Koliwad; Charles Harris; Robert V Farese
Journal:  J Lipid Res       Date:  2008-08-29       Impact factor: 5.922

10.  Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2).

Authors:  Kentaro Futatsugi; Daniel W Kung; Suvi T M Orr; Shawn Cabral; David Hepworth; Gary Aspnes; Scott Bader; Jianwei Bian; Markus Boehm; Philip A Carpino; Steven B Coffey; Matthew S Dowling; Michael Herr; Wenhua Jiao; Sophie Y Lavergne; Qifang Li; Ronald W Clark; Derek M Erion; Kou Kou; Kyuha Lee; Brandon A Pabst; Sylvie M Perez; Julie Purkal; Csilla C Jorgensen; Theunis C Goosen; James R Gosset; Mark Niosi; John C Pettersen; Jeffrey A Pfefferkorn; Kay Ahn; Bryan Goodwin
Journal:  J Med Chem       Date:  2015-09-24       Impact factor: 7.446
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