Extended Data Fig. 7: Further in vivo characterization of compound 4.
From: Mutant-selective AKT inhibition through lysine targeting and neo-zinc chelation
a, Individual growth curves of LAPC4-CR xenografts related to Fig. 4a. LAPC4-CR tumor-bearing mice (athymic nu/nu) were randomized to vehicle (n = 10) or compound 4 treatment groups (30 mg kg–1, BID, IP, n = 12). b, Individual tumor growth curves (a) were integrated (AUC, mm3) over the 18 day study. Vehicle, n = 10; compound 4, n = 12 (mean ± s.e.m.). Student’s t-test (two-tailed, unpaired, parametric) was used to calculate the P value without adjustments for multiple comparison tests. c, Percentage change in mouse body weights during the LAPC4-CR tumor growth inhibition study. Vehicle, n = 10; compound 4, n = 12 (mean ± s.e.m.). d, LAPC4-CR tumor-bearing mice (athymic nu/nu) were randomized to vehicle or ARQ092 treatment groups (100 mg kg–1, PO, QD), n = 10. Tumor volumes (mean ± s.e.m.) and body weights (mean ± s.e.m.) were measured on the indicated days. The humane endpoint was 20% body weight loss and the ARQ092 arm was terminated when 50% of the animals in the group reached this threshold. e, Percentage change in mouse body weights during the HBCx-2 tumor growth inhibition study (see Fig. 4c). n = 8, mean ± s.e.m., ns = not significant. Adjusted P values were calculated for the final day measurements relative to the vehicle using an ordinary one-way ANOVA with Dunnett’s multiple comparison test. f, BT-474 tumor-bearing mice (athymic nude) were randomized to vethicle (BID, IP injection), compound 4 (30 mg kg–1, BID, IP injection), ARQ092 (100 mg kg–1, QD, PO) or capivasertib (150 mg kg–1, BID, PO) treatment groups (n = 10). Tumor volumes (mean ± s.e.m) were measured on the indicated days. Adjusted P values were calculated for the final day measurements relative to the vehicle using an ordinary one-way ANOVA with Dunnett’s multiple comparison test. g, Percentage change in mouse body weights during the BT-474 tumor growth inhibition study. n = 10, mean ± s.e.m. Adjusted P values were calculated for the final day measurements relative to the vehicle using an ordinary one-way ANOVA with Dunnett’s multiple comparison test. Apparently missing errors bars indicate that the error is too small to be visualized.
