FKBP12 PROTAC dTAG-13

FKBP12 PROTAC dTAG-13 (dTAG-13) is a FKBP12^F36V PROTAC degrader and a PXR partial agonist. FKBP12 PROTAC dTAG-13 induces ubiquitination and proteasomal degradation of proteins tagged with FKBP12^F36V, without degrading wild-type FKBP12 or un-fused PXR. It weakly promotes the recruitment of SRC-1, strongly inhibits the interaction between NCoR and PXR, and upregulates the expression of CYP3A4 and other drug metabolism-related genes. FKBP12 PROTAC dTAG-13 is applicable to research related to breast cancer and leukemia^[1][2][3]. IC50 & Target:FKBP12^F36V[1]
BRD4^[1]
PROTAC^[1] In Vitro:FKBP12 PROTAC dTAG-13 (0.00001-100 μM; 24 h) marginally modulates basal PXR-coregulator interactions but potently disrupts SPA70-induced PXR-NCoR complex formation in transfected HepG2 cells^[1].
FKBP12 PROTAC dTAG-13 (10 μM, 0.3-30 μM; 24 h) acts as a partial PXR agonist to induce endogenous CYP3A4 expression in SNU-C4 and SNU719 cells, and partially inhibits Rifampicin (HY-B0272)-mediated CYP3A4 induction in SNU719 cells, without altering PXR or GAPDH RNA levels^[1].
FKBP12 PROTAC dTAG-13 (0.1-10 μM; 30 min) potently induces CRBN-FKBP12^F36V-PXR complex formation but does not induce CRBN-unfused PXR complex formation in transfected HepG2 cells^[1].
FKBP12 PROTAC dTAG-13 (0.00001-100 μM; 24 h) retains partial agonist/antagonist activity for unfused PXR in transfected HepG2 cells regardless of CRBN co-expression, but its agonist activity is abolished and antagonistic activity is enhanced for FKBP12^F36V-PXR when CRBN is co-overexpressed^[1].
FKBP12 PROTAC dTAG-13 (1 µM; 1 h, 24 h, 48 h, 72 h) induces rapid, proteasome- and CRBN-dependent degradation of FKBP12^F36V-KRAS^G12V in NIH/3T3 cells, rapidly reversing KRAS^G12V-driven signaling, morphology, cell cycle, and proliferation to basal cellular states^[3].
FKBP12 PROTAC dTAG-13 (16 h) potently induces degradation of luciferase-FKBP12^F36V in MV4;11 cells, as measured by reduced bioluminescence^[3]. In Vivo:FKBP12 PROTAC dTAG-13 (20 mg/kg; i.p.; single dose) exhibits rapid absorption, sustained systemic exposure for 4 hours, broad tissue distribution (excluding the brain), extensive phase I metabolism, and efficient clearance in male C57BL/6NJ mice, supporting its use for short-term, peripheral targeted protein degradation studies^[2].
dTAG-13 (25 mg/kg; i.p.; single dose) induces significant, rapid, and reversible degradation of luciferase-FKBP12^F36V in a mouse disseminated leukemia model^[3].