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. Author manuscript; available in PMC: 2018 Feb 23.
Published in final edited form as: Cell. 2017 Feb 23;168(5):878–889.e29. doi: 10.1016/j.cell.2017.02.006

Figure 3. 3144 has RAS-dependent lethality.

Figure 3

(A) (left panel) Inhibition of RAS expression in DLD-1 cells transfected with siRNAs targeting HRAS, NRAS and KRAS (si-panRAS) or a non-targeting siRNA control. Total Ras expression was determined with a pan-RAS antibody, as well as actin abundance. The total RAS abundance, normalized to actin abundance, is indicated. (middle and right panels) The concentration-dependent effects of 3144 and MG132 on DLD1 cells transfected with either si-panRAS or siNT was measured using Cell Titer Glo. (B) The effect of 3144 (left panel) and vemurafenib (right panel) on viability and growth of mouse embryo fibroblasts (MEFs) was measured at the indicated concentrations using Alamar blue. All compound measurements were performed in duplicate. Black line = Kraslox/lox, Hras−/−, Nras−/− RERTnert/ert MEFs; red line = BRAFV600E-CAAX; Kras−/−, Hras−/−, Nras−/− RERTnert/ert MEFs. (C) The effect of 3144 was tested at the indicated concentrations in cultured patient-derived T-ALL samples. PDTALL6, 9, 13 and 19 = wt NRAS, PDTALL22 = NRASG13V, PDTALL26 = NRASG13D. See also Figure S3 and Supporting Information.