Fig. 1: dTAG^V-1 is an exclusively selective degrader of FKBP12^F36V-tagged proteins.

a Schematic depiction of the dTAG system using VHL-recruiting dTAG molecules. VHL-recruiting dTAG molecules promote ternary complex formation between the FKBP12^F36V-tagged target protein and E3 ubiquitin ligase complex, inducing target protein ubiquitination and degradation. b Chemical structures of dTAG^V-1 and dTAG^V-1-NEG. c DMSO-normalized ratio of Nluc/Fluc signal of 293FT FKBP12^WT-Nluc or FKBP12^F36V-Nluc cells treated with dTAG^V-1 or dTAG^V-1-NEG for 24 h. Data are presented as mean ± s.d. of n = 4 biologically independent samples and are representative of n = 3 independent experiments. d Protein abundance after treatment of PATU-8902 LACZ-FKBP12^F36V clone with 500 nM dTAG^V-1 for 4 h compared to DMSO treatment. Volcano plots depict fold change abundance relative to DMSO versus P value derived from a two-tailed Student’s t-test. Fold change values and significance designations derived from a two-tailed Student’s t-test and a permutation-based FDR estimation are provided in Supplementary Data 2. Data are from n = 3 biologically independent samples. e Immunoblot analysis of PATU-8902 LACZ-FKBP12^F36V clone co-treated with DMSO, THAL-SNS-032, and/or dTAG^V-1 as indicated for 24 h. Data is representative of n = 3 independent experiments. Source data for c and e are provided as a Source Data file.