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FKBP12 PROTAC dTAG-13 (dTAG-13), a PROTAC-based heterobifunctional degrader, is a selective degrader of FKBP12 with expression of FKBP12F36V in-frame with a protein of interest. FKBP12 PROTAC dTAG-13 effectively engages FKBP12 and CRBN, thereby selectively degrading FKBP12.

TAG-13 (1-1000 nM; 4 hours; 293FT cells) treatment potently reduces FKBP12-Nluc levels in 293FT cell, indicating the requirement of CRBN for the observed effects.
Treatment of MV4;11 cells expressing BRD4(short)-FKBP12 with dTAG-13 leads to robust degradation of BRD4. dTAG-13 treatment leads to rapid degradation of BRD4 within one hou. dTAG-13 treatment leads to rapid and potent degradation of the BRD4 fusion chimera in the heterozygous and homozygous knock-in clones, with no effect on endogenous FKBP12.

Following bone marrow engraftment of MV4;11 cells expressing luc-FKBP12F36V in mice, the bioluminescent signal after vehicle or dTAG-13 administration is monitored. A significant, rapid, and durable effect on bioluminescent signal is observed four hours after dTAG-13 administration, indicating effective degradation of luc-FKBP12F36V. Twenty-eight hours following the final treatment, the recovery of cellular bioluminescence to levels comparable between vehicle and dTAG-13 treatment groups is observed.

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