Extended Data Fig. 8: FK-Dasatinib is a FKBP12-dependent Src family kinase inhibitor with long cellular retention time.

a, Structures of Dasatinib and FK-Dasatinib. b, Proposed working model for FKBP-dependent kinase inhibitors. c, Inhibition of Src, Csk and DDR2 kinases by Dasatinib and FK-Dasatinib in the absence or presence of supplemented 10 µM recombinant FKBP12 protein (n = 2, data are presented as individual points). d, Inhibition of K562 cell proliferation by Dasatinib and FK-Dasatinib, in the presence or absence of 10 µM RapaBlock (n = 3, data are presented as mean values +/− SD). e, Jurkat cells were stimulated with anti-CD3 antibody (OKT3) in the presence of dasatinib, FK-dasatinib, and/or RapaBlock and analyzed by immunoblot. COX IV is a loading control. Data is representative of two independent experiments. f, Jurkat cells were pulse-treated with Dasatinib (100 nM) or FK-Dasatinib (100 nM) for 1 h, then drugs were washed out and cells were incubated in drug-free media for various amounts of time, stimulated with anti-CD3 antibody (OKT3) for 5 min and analyzed by immunoblot. Results shown are representative of three independent experiments. COX-IV is a loading control. For gel source data, see Supplementary Fig. 1. g, inhibition of 476 purified kinases by Dasatinib (10 nM) or FK-Dasatinib (10 nM) in the presence of 10 µM recombinant FKBP12 protein (n = 1). See Supplementary Table 1 for a full list of kinase inhibition data. h, kinase profiling of Dasatinib (100 nM Dasatinib) or FK-Dasatinib (100 nM) in Jurkat cells using the covalent occupancy probe XO44. Results shown are representative of two independent experiments.