Description
SAfit2 is a potent inhibitor of FK506-binding protein 51 (FKBP51; K
i = 6 nM). It is highly selective for FKBP51 over FKBP52 (K
i = >50,000 nM) and has increased brain permeability in comparison to SAfit1. SAfit2 (20 mg/kg) enhances HPA axis suppression in mice by decreasing plasma corticosterone levels to a greater extent than in control mice following dexamethasone administration. It also does not increase plasma corticosterone levels as high as in control mice following subsequent administration of corticotropin-releasing factor (CRF; ). It decreases the time spent immobile in the forced swim test and increases the time spent in the open arms of the elevated plus maze, indicating antidepressant-like and anxiolytic-like activity, respectfully.
Uses
SAFit2 is a highly selective inhibitor of FKBP51. The selective inhibition of FKBP51, using SAFit1(S139583) & SAFit2 , has shown to enhances neurite elongation in neuronal cultures and improves neuroendocrine feedback and stress-coping behavior in mice.
in vivo
It is found that 30 days of SAFit2 administration leads to a reduction in body weight under both control and high-fat diet (HFD) conditions. SAFit2 significantly increases phosphorylated AKT2 and AS160 in EDL muscle and likewise increases expression of GLUT4 at the membrane in soleus muscle[2]. When SAFit2 is applied 1 h before testing, no alterations in anxiety-related behavior are observed. However, SAFit2 treatment induces an anxiolytic phenotype in mice injected 16 h prior testing, which is reflected in a significantly increased open arm time in the elevated plus maze (EPM) (z=-2.183, p<0.05). SAFit2 treatment leads to a significantly reduced latency to enter the lit compartment (z=-2 to 265, p<0.05), as well as a significantly increased distance traveled (t(20)=-2.371, p<0.05) in the lit compartment[3].
References
[1] STEFFEN GAALI. Selective inhibitors of the FK506-binding protein 51 by induced fit[J]. Nature chemical biology, 2014, 11 1: 33-37. DOI:
10.1038/nchembio.1699[2] JAKOB HARTMANN. Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic Properties.[J]. Journal of Neuroscience, 2015, 35 24: 9007-9016. DOI:
10.1523/jneurosci.4024-14.2015
