Figure 2.

Antitumor efficacy of CHK1/2 inhibitors in patient-derived TSC2-deficient tumors. (A) Dose–response curves for AZD7762 in 621-102 or UMB1949 cell lines after 72 h of treatment. Data are presented as mean ± s.e.m. (n = 3) after normalization to control, and the best fit EC₅₀ is indicated. (B) Relative viability measurements of 621-102 or UMB1949 cells 72 h after siRNA knockdown of either CHK1 or CHK2. (C) UMB1949 cell line tumorgraft tumor volume in NSG mice. After tumors reached 400 ± 25 mm³ in volume, mice were treated (i.p. injection) 5× per week with either vehicle (n = 9) or AZD7762 (12.5 mg/kg, n = 9); data presented as mean ± 95% confidence interval. (D) Western blot of tumor lysates from UMB1949 tumorgrafts treated with either vehicle or AZD7762. Lysates were probed for phospho-markers of CHK1 (pS296 and pS345) and total CHK1 used as loading control; CHKi-1 and CHKi-2 indicate two AZD7762-treated tumors from panel (C).