| Autor: |
Taeyoung Yoon, Kevin B. Clairmont, Yongjin Gong, Qing Yang, Marlene Juedes, Andrew Tyler, Michael H. Serrano-Wu, Theresa Cosker, Moo Je Sung, Tara L. Mullarkey, Lisha Li, Gary M. Coppola, Alan D. Neubert, Thomas Daniels, Erik C. Rocheford, Renee Commerford, Ying Hou, Ricardo E. Chatelain, Monish Jain, Brian K. Hubbard |
| Rok vydání: |
2012 |
| Předmět: |
|
| Zdroj: |
ACS Medicinal Chemistry Letters. 3:411-415 |
| ISSN: |
1948-5875 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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