SERRANOWU MICHAEL H; COPPOLA GARY M; GONG YONGJIN; NEUBERT ALAN D; CHATELAIN RICARDO; CLAIRMONT KEVIN B; COMMERFORD RENEE; COSKER THERESA; DANIELS THOMAS; HOU YING; JAIN MONISH; JUEDES MARLENE; LI LISHA; MULLARKEY TARA; ROCHEFORD ERIK; SUNG MOO JE; TYLER ANDREW; YANG QING; YOON TAEYOUNG; HUBBARD BRIAN K
[摘要]：High DGAT1 expression levels in the small intestine highlight the critical role this enzyme plays in nutrient absorption. Identification of inhibitors which predominantly inhibit DGAT1 in the gut is an attractive drug discovery strategy with anticipated benefits of reduced systemic toxicity. In this report we describe our discovery and optimization of DGAT1 inhibitors whose plasma exposure is minimized by the action of transporters, including the P-glycoprotein transporter. The impact of this unique absorption profile on efficacy in rat and dog efficacy models is presented.
