Discovery of a benzimidazole series as the first highly potent and selective ACSL1 inhibitors.
Bioorg Med Chem Lett
; 33: 127722, 2021 02 01.
Article
in En
| MEDLINE
| ID: mdl-33285268
ABSTRACT
Long-chain acyl-CoA synthetase-1 (ACSL1), an enzyme that catalyzes the synthesis of long-chain acyl-CoA from the corresponding fatty acids, is believed to play essential roles in lipid metabolism. Structure activity relationship studies based on HTS hit compound 1 delivered the benzimidazole series as the first selective and highly potent ACSL1 inhibitors. Representative compound 13 exhibited not only remarkable inhibitory activity against ACSL1 (IC50 = 0.042 µM) but also excellent selectivity for the other ACSL isoforms. In addition, compound 13 demonstrated an in vivo suppression effect against the production of long-chain acyl-CoAs in mouse.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzimidazoles
/
Coenzyme A Ligases
/
Enzyme Inhibitors
/
Drug Discovery
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2021
Document type:
Article