Fig. 3. A947-mediated inhibition of cell proliferation in SMARCA4-mutant NSCLC cell lines.

a Viability of NCI-H1944 following 7 days of treatment with a dose response of A947 or binding-defective epimers. Error bars represent mean ± SD from n = 3 biologic replicates. b Immunoblots of SMARCA2, SMARCA4 and PBRM1 levels across a panel of NSCLC cell lines defined by SMARCA4 gene mutation status. β-tubulin serves as a loading control. Data are representative of 2 independent experiments. c Effect of A947 treatment on the growth of 30 lung cancer cell lines defined by SMARCA4 or SMARCA2 status, represented as the concentration of A947 required to inhibit growth by 50% (IC₅₀) following 7 days of treatment. Individual cell line IC₅₀’s were determined from n = 3 biologic replicates. Median IC₅₀’s across models defined by mutational status are indicated by the black line. Significance was assessed by a two-tailed, Mann Whitney test. Asterick indicates p = 0.0003 d Cell cycle distribution following 48 h treatment of a dose response of A947 across 4 SMARCA4-mutant, 2 SMARCA4-wt and one SMARCA2-deficient NSCLC cell lines. Aphidicolin (Aph, 1 μM) treatment served as a control to block entry into S phase for the SMARCA4-wt and SMARCA2-deficient models. Error bars represent mean ± SD from n = 3 biologic replicates. e Log₂-transformed fold change in mRNA expression values, as measured by RNA-seq, in HCC2302 cells treated for 96 h with A947 compared to control DMSO treated cultures (x-axis), as well as HCC2302-shSMARCA2 cells treated with doxycycline for 168 h compared to HCC2302 cells expressing a non-targeted control shRNA (shNTC). RNAseq data is representative of triplicated cultures. The correlation was calculated by the Pearson coefficient. p = 2.2e−16. Source data are provided as a Source Data file.