Extended Data Fig. 2. ESK981 inhibits the growth of diverse preclinical models of prostate cancer in vivo.

(a) Schematic illustration of the VCaP CRPC mouse xenograft experimental design. To generate castration-resistant VCaP, parental VCaP cells were injected subcutaneously into both flanks of intact male mice. When average VCaP tumors reached 200 mm³, mice were surgically castrated and VCaP tumors regressed due to loss of androgen. Castration-resistant VCaP tumors developed as VCaP tumors grew back to the size of pre-castration. Castration-resistant VCaP tumors were then randomized into three groups and treated with vehicle, 30 mg/kg, or 60 mg/kg ESK981 p.o., oral gavage.

(b) Representative IHC images for proliferation marker Ki67 are shown after treatment with the indicated drugs for five days in VCaP tumors (left). Quantification of positive Ki67 percentage is shown on the right (right). Data were analyzed by two-tailed unpaired t test and presented as mean ± SEM. N=4 tumors per group. P-value indicated.

(c) Representative individual tumors from vehicle and ESK981 groups in AR⁺ and ERG⁺ prostate PDX MDA-PCa-146-12 (left). Representative IHC showing Ki67 staining for vehicle and 30 mg/kg ESK981 groups of MDA-PCa-146-12 tumors (right) from three independent experiments.

(d) Representative individual tumors from vehicle and ESK981 groups of DU145 tumors (left). Representative IHC showing Ki67 staining for the vehicle and 30 mg/kg ESK981 groups of DU145 tumors (right) from three independent experiments.