SAFit2

SAFit2 is a potent and selective small-molecule inhibitor of FK506-binding protein 51 (FKBP51), a key regulator of the glucocorticoid receptor signaling pathway involved in the stress response, chronic pain, metabolic syndrome, and depression. SAFit2 acts by binding to FKBP51 with high affinity (Ki = 6 nM), exhibiting remarkable selectivity over the related protein FKBP52. It has demonstrated efficacy in preclinical models for reducing neuroinflammation, mechanical hypersensitivity (pain), obesity, and alcohol consumption. SAFit2’s pharmacologic activity includes restoration of lipid metabolism, reduction of neuroinflammation (via NF-κB inhibition), decreased phosphorylation and activity of the TRPV1 channel, and normalization of stress-induced behavioral changes in rodents. Developed as a research tool and proof-of-concept compound, it currently serves as the gold standard for FKBP51 pharmacology in experimental settings, although it has not been advanced for clinical use due to its large molecular size and suboptimal drug-like properties.[1][3][5][6][8]

Other names

selective antagonist of FKBP51 by induced fit