Fig. 3

Activity of ARTADIs against constitutively active AR-V7 splice variant. a Table showing IC₅₀ values for the V7BS3-luciferase reporter activities and clonogenic assay of LNCaP95 cells that are both driven by AR-V7 compared to androgen-induced full-length AR driven reporters. b Dose response curves of AR-V7 driven V7BS3-luciferase reporter activities in LNCaP cells transiently transfected to express AR-V7 protein. c Survival curves using the colony formation assay with LNCaP95 cells exposed to compounds. Data represents mean ± SEM, n ≥ 3. d Left panel - temporal tumor growth of subcutaneous LNCaP95-D3 xenografts in castrated NSG mice receiving vehicle (VEH), enzalutamide (ENZA, 10 mg/kg), or BU130 (30 mg/kg) daily by oral gavage. Right panel shows the final tumor volumes. e Body weight changes for each mouse represented in Fig. 3d. f Left panel - temporal tumor growth of subcutaneous VCaP-ENZR xenografts in castrated NSG mice receiving vehicle (VEH), enzalutamide (ENZA, 10 mg/kg), or BU170 (30 mg/kg) daily by oral gavage. Right panel shows the final tumor volumes. g Body weight changes for each mouse represented in Fig. 3f. h Dose-response curves of transcript levels of AR3/AR-V7 regulated genes from LNCaP95 cells, and i VCaP cells treated with enzalutamide, EPI-002 (ralaniten), BU3-12, BU130 or BU170 for 48 h in steroid-depleted media. DMSO was used as reference for normalization. Data presented as mean ± SEM (n = 4 independent experiments). j Table showing IC₅₀ values to block endogenous expression of the genes shown in h, i. The sum-of-squares F test was performed to compare IC50’s for each inhibitor against EPI-002. n.s., not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. ND: not detected. N/A: not available