FKBP12 PROTAC dTAG-7

FKBP12 PROTAC dTAG-7 (dTAG-7) is a FKBP12^F36V PROTAC degrader. FKBP12 PROTAC dTAG-7 binds FKBP12^F36V and CRBN to form a complex, mediating degradation via the ubiquitin-proteasome system. FKBP12 PROTAC dTAG-7 mediates the degradation of FKBP12^F36V-tagged nuclear and cytoplasmic proteins, including BRD4, HDAC1, EZH2, MYC, PLK1, KRAS^G12V, and antigen fusion proteins. FKBP12 PROTAC dTAG-7 enhances MHC class I antigen presentation. FKBP12 PROTAC dTAG-7 is applicable to leukemia-related research^[1][2]. IC50 & Target:FKBP12^F36V[1]
BRD4^[1]
PROTAC^[1] In Vitro:The FKBP12 PROTAC dTAG-7 effectively induces heterodimerization of purified CRBN-DDB1 and FKBP12^F36V proteins in cell-free AlphaScreen assays^[1].
The FKBP12 PROTAC dTAG-7 (100 nM) induces CRBN-dependent degradation of the FKBP12^F36V-Nluc fusion protein in 293FTWT cells, but has no effect on endogenous FKBP12^WT or the FKBP12^WT-Nluc fusion protein, and shows no activity in CRBN-deficient 293FT^CRBN−/− cells^[1].
The FKBP12 PROTAC dTAG-7 (50 nM) efficiently degrades a variety of FKBP12^F36V fusion proteins (FKBP12^F36V-KRAS^G12V, FKBP12^F36V-EZH2, HDAC1-FKBP12^F36V, MYC-FKBP12^F36V, PLK1-FKBP12^F36V, BRD4 (short)-FKBP12^F36V) in MV4;11 cells, and degrades the endogenously tagged FKBP12^F36V-BRD4 fusion protein in homozygous knock-in 293T cells^[1].
The FKBP12 PROTAC dTAG-7 (0.01-5 μM; 18 h) induces proteasome-dependent, concentration- and time-dependent degradation of GFP-S8L-F12 in mouse macrophage BMC-2 cells^[2].
The FKBP12 PROTAC dTAG-7 (0.015-5 μM; 18 h) specifically reduces GFP-specific fluorescence in mouse macrophage BMC-2 cells in a concentration-dependent manner (indicating degradation of mature GFP-S8L-F12), and its effect is fully reversible within 8 h after compound washout^[2].
The FKBP12 PROTAC dTAG-7 (1 μM; 0-24 h) induces antigen-specific, FKBP12-dependent enhancement of H-2K^b/S8L MHC class I presentation in mouse macrophage BMC-2 cells, with the peak of presentation observed at 2 h after treatment with 1 μM dTAG-7^[2].
The FKBP12 PROTAC dTAG-7 (1 μM; 0-30 h) induces rapid degradation of GFP-S8L-F12 and enhances the presentation of H-2K^b/S8L class I MHC molecules in mouse dendritic cell line DC2.4 and mouse fibrosarcoma cell line MC57G^[2].
The FKBP12 PROTAC dTAG-7 (1 μM; 2-6 h) enhances the presentation of H-2K^b/S8L class I MHC molecules in GFP-S8L-F12-expressing mouse macrophage BMC-2 cells and mouse fibrosarcoma MC57G cells^[2].