Discovery of Small Molecule Isozyme Non-specific Inhibitors of Mammalian Acetyl-CoA Carboxylase 1 and 2
Journal Article
·
· Bioorganic and Medicinal Chemistry Letters
Screening Pfizer's compound library resulted in the identification of weak acetyl-CoA carboxylase inhibitors, from which were obtained rACC1 CT-domain co-crystal structures. Utilizing HTS hits and structure-based drug discovery, a more rigid inhibitor was designed and led to the discovery of sub-micromolar, spirochromanone non-specific ACC inhibitors. Low nanomolar, non-specific ACC-isozyme inhibitors that exhibited good rat pharmacokinetics were obtained from this chemotype.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1019899
- Report Number(s):
- BNL-95745-2011-JA; TRN: US201115%%535
- Journal Information:
- Bioorganic and Medicinal Chemistry Letters, Vol. 20, Issue 7; ISSN 0960-894X
- Country of Publication:
- United States
- Language:
- English
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