| Literature DB >> 22263872 |
Vince S C Yeh1, David W A Beno, Sevan Brodjian, Michael E Brune, Steven C Cullen, Brian D Dayton, Madhup K Dhaon, Hugh D Falls, Ju Gao, Nelson Grihalde, Philip Hajduk, T Matthew Hansen, Andrew S Judd, Andrew J King, Russel C Klix, Kelly J Larson, Yau Y Lau, Kennan C Marsh, Scott W Mittelstadt, Dan Plata, Michael J Rozema, Jason A Segreti, Eric J Stoner, Martin J Voorbach, Xiaojun Wang, Xili Xin, Gang Zhao, Christine A Collins, Bryan F Cox, Regina M Reilly, Philip R Kym, Andrew J Souers.
Abstract
A high-throughput screen against human DGAT-1 led to the identification of a core structure that was subsequently optimized to afford the potent, selective, and orally bioavailable compound 14. Oral administration at doses ≥0.03 mg/kg significantly reduced postprandial triglycerides in mice following an oral lipid challenge. Further assessment in both acute and chronic safety pharmacology and toxicology studies demonstrated a clean profile up to high plasma levels, thus culminating in the nomination of 14 as clinical candidate ABT-046.Entities:
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Year: 2012 PMID： 22263872 DOI： 10.1021/jm201524g
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446