SAFit1

SAFit1 is a first-in-class, highly selective small molecule inhibitor of the immunophilin FKBP51 (FK506-binding protein 51). It was developed using an induced-fit strategy to achieve over 10,000-fold selectivity for FKBP51 over its closely related homolog FKBP52, a feat previously difficult due to the high structural similarity between the two proteins. FKBP51 acts as a co-chaperone for the glucocorticoid receptor and is a key regulator of the stress response; its dysregulation is linked to mood disorders, post-traumatic stress disorder (PTSD), chronic pain, and metabolic diseases. In oncology, SAFit1 has demonstrated the ability to downregulate PD-L1 expression in glioblastoma and melanoma models, suggesting a role in enhancing anti-tumor immunity and overcoming chemoresistance.

Other names

Synthetic Antagonist of FKBP51 by Induced fit 1