FKBP

FKBP ligands bind FK506-binding proteins (FKBPs), a family of peptidyl-prolyl cis-trans isomerases. In 1989 the receptor for the immunosuppressant FK506 (tacrolimus) was shown to be such an isomerase, now known as FKBP12. Pimecrolimus is a related macrolactam that also binds FKBP12 and inhibits calcineurin. SAFit1 and SAFit2 selectively inhibit FKBP51 through an induced-fit binding mode reported in 2015. Shield-1 stabilizes fusions to a destabilized FKBP12 domain, a method described in 2006 for rapid, reversible control of protein levels. AP1867 binds the engineered mutant FKBP12(F36V), and FKBP12 PROTAC dTAG-7 uses this ligand to degrade tagged proteins in the degradation tag (dTAG) system. Rimiducid and zapalog are chemical inducers of dimerization for FKBP fusion proteins.