FIGURE 7 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Year: 2023
Type: other
Abstract: Treatment of mice with KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels and induces apoptosis in KRAS G12D PDXs from patients with pancreatic cancer. A, Tumor biopsies from patient G160 were subcutaneously implanted into NSG mice as described in Materials and Methods, and when the average tumor volume reached 200 mm3, the mice were treated either with vehicle (mice V1, V2, V3) or 5 mpk KRB-456 (mice KRB1, KRB2, KRB3) as described in Materials and Methods. Two hours after treatment, tumors were harvested and lysates were processed for Western blotting as described in Materials and Methods. * and ** designates blots from different gels. B and C, Quantification of the Western blots. P values were determined by Student t test, * designates P < 0.05. The actual P values were 0.016 (P-MEK/MEK), 0.010 (P-ATK(S473)/AKT), 0.012 (P-ATK(T308)/AKT), 0.037 (P-S6/S6), 0.069 (P-ERK/ERK), 0.097 (CASPASE3/b-ACTIN), and 0.019 (PARP/b-ACTIN). Error bars represent SE.
Authors: Aslamuzzaman Kazi, Alok Ranjan, Vasantha Kumar M.V., Bogos Agianian, Martin Garcia Chavez, Vignesh Vudatha, Rui Wang, Rajanikanth Vangipurapu, Liwei Chen, Perry Kennedy, Karthikeyan Subramanian, Jonathan C.K. Quirke, Francisca Beato, Patrick W. Underwood, Jason B. Fleming, Jose Trevino, Paul J. Hergenrother, Evripidis Gavathiotis, Said M. Sebti
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4390347556