Fig. 2: dTAG^V-1 is an in vivo-compatible degrader of FKBP12^F36V-tagged proteins.

a Immunoblot analysis of PATU-8902 FKBP12^F36V-KRAS^G12V; KRAS^−/− clone treated with DMSO, dTAG^V-1, or dTAG^V-1-NEG for the indicated time-course. b Immunoblot analysis of 293T^WT FKBP12^F36V-KRAS^G12V or 293T^VHL-/- FKBP12^F36V-KRAS^G12V cells treated with DMSO or the indicated dTAG molecules for 24 h. Data in a, b are representative of n = 3 independent experiments. c DMSO-normalized antiproliferation of PATU-8902 LACZ-FKBP12^F36V or FKBP12^F36V-KRAS^G12V; KRAS^-/- clones treated with dTAG^V-1 or dTAG^V-1-NEG for 120 h. Cells were cultured as ultra-low adherent 3D-spheroid suspensions. Data are presented as mean ± s.d. of n = 4 biologically independent samples and are representative of n = 3 independent experiments. d Bioluminescent imaging to evaluate degradation of luciferase-FKBP12^F36V in mice was performed daily as follows: day 0 to establish baseline signal, day 1–3 to monitor luciferase-FKBP12^F36V signal 4 h after vehicle or dTAG molecule treatment (T), day 4 to monitor duration of luciferase-FKBP12^F36V signal 28 h after third and final vehicle or dTAG molecule treatment. Total flux for each mouse is depicted. Data are presented from vehicle (n = 5 biologically independent mice at day 0–4), dTAG-13 (n = 5 biologically independent mice at day 0–3; n = 4 biologically independent mice at day 4) or dTAG^V-1 (n = 5 biologically independent mice at day 0–4) treated mice. P values are derived from a two-tailed Welch’s t-test (*P < 0.05, **P < 0.01) and are provided as a Source Data file. Source data for a–d are provided as a Source Data file.