SAFit2 is a highly effective and selective fk506 binding protein 51(FKBP51) inhibitor (Ki: 6 nM). SAFit2 can enhance AKT2-AS160 binding and participate in the downstream response of glucocorticoid release in vivo, and is a candidate compound for the treatment of obesity, chronic pain, depression and anxiety.

SAFit2 treatment enhances pAKT2 expression in the soleus and EDL muscle, as well as pAS160 expression in the EDL muscle of WT cells, while FKBP51 antagonism has no impact on 51KO cells. Additionally, SAFit2 treatment leads to an increase in membrane-bound GLUT4 expression in primary EDL myotubes from WT mice, whereas no such effect is observed in 51KO mice.[1]

SAFit2 significantly enhances phosphorylation of AKT2 and AS160 in the EDL muscle, while also increasing GLUT4 expression at the muscle membrane in the soleus. Administration of SAFit2 induces an anxiolytic phenotype in mice tested 16 hours after injection, as evidenced by a significant increase in open arm time in the elevated plus maze (EPM) (z=-2.183, p<0.05). SAFit2 treatment results in a significantly decreased latency to enter the lit compartment (z=-2 to 265, p<0.05), as well as a notable increase in distance, traveled (t(20)=-2.371, p<0.05) within the lit compartment. It has been observed that 30 days of SAFit2 administration leads to reduced body weight in both control and high-fat diet conditions. When SAFit2 is administered 1 hour before testing, no changes in anxiety-related behavior are detected.[1][2]