dFKBP-1 

dFKBP-1 is a potent and PROTAC-based FKBP12 degrader. dFKBP-1 incorporates the ligand SLF (HY-114872) of FKBP12, the Thalidomide based Cereblon ligand and a linker^[1].

dFKBP-1 potently decreases FKBP12 abundance in MV4;11 cells, leading to over 80% reduction of FKBP12 at 0.1 μM and 50% reduction at 0.01 μM. As with dBET1, destabilization of FKBP12 by dFKBP-1 is rescued by pre-treatment with Carfilzomib, MLN4924, free SLF or free Thalidomide. Cereblon (CRBN)-dependent degradation is established using previously published isogenic 293FT cell lines which are wild-type (293FT-WT) or deficient (293FT-CRBN^−/−) for CRBN. Treatment of 293FT-WT cells with dFKBP-1 induces potent, dose-dependent degradation of FKBP12, whereas 293FT-CRBN^−/− are unaffected^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

1009.11

Solid

C₅₃H₆₄N₆O₁₄

1799711-22-0

O=C([C@H]1N(C(C(C(C)(C)CC)=O)=O)CCCC1)O[C@@H](C2=CC=CC(NC(CCC(NCCCCNC(COC3=CC=CC(C(N4C(CC5)C(NC5=O)=O)=O)=C3C4=O)=O)=O)=O)=C2)CCC6=CC=C(OC)C(OC)=C6

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

• [1]. Winter GE, et al. DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science. 2015 Jun 19;348(6241):1376-81.  [Content Brief]