Discovery of Novel Agonists and Antagonists of the Free Fatty Acid Receptor 1 (FFAR1) Using Virtual Screening

• Published in: Journal of medicinal chemistry Vol. 51; no. 3; pp. 625 - 633
• Main Authors: Tikhonova, Irina G, Sum, Chi Shing, Neumann, Susanne, Engel, Stanislav, Raaka, Bruce M, Costanzi, Stefano, Gershengorn, Marvin C
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14.02.2008
• Subjects: Binding Sites; Biological and medical sciences; Calcium - metabolism; Cell Line; Databases, Factual; Drug Partial Agonism; General and cellular metabolism. Vitamins; Humans; Ligands; Medical sciences; Mutation; Pharmacology. Drug treatments; Protein Conformation; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - chemistry; Stereoisomerism; Structure-Activity Relationship; Thiadiazoles - chemistry; Thiadiazoles - pharmacology; Thiazolidines - chemistry; Thiazolidines - pharmacology; Agonist; GPR40 receptor; Thiazole derivatives; Site directed mutagenesis; Virtual screening; Free fatty acid; Insulin; Structure function relationship; Non steroidal antiinflammatory agent; Benzoic acid derivatives; Structure activity relation; G protein coupled receptor; Binding mode; Carboxamide; Arylpropionic acid derivatives; Benzamide derivatives; Antagonist; G protein

The G-protein-coupled receptor free fatty acid receptor 1 (FFAR1), previously named GPR40, is a possible novel target for the treatment of type 2 diabetes. In an attempt to identify new ligands for this receptor, we performed virtual screening (VS) based on two-dimensional (2D) similarity, three-dim...