(A) Anti-proliferative activity of SHR8443 against a panel of cancer cell lines with different tissues of origin and genetic backgrounds. Tumor cell lines harboring a PIK3CA mutation (♦), HER2 amplification (●), PTEN deficiency (□), or RAS/RAF mutation (*) were treated with different concentrations of SHR8443 for 72 h. Cell viability was determined by SRB assay. IC50 values were presented as means ± SD of three independent experiments. (B) Melanoma cell lines A375, A375/TR (trametinib-resistant), and A375/DR (dabrafenib-resistant) were treated with different concentrations of SHR8443, dabrafenib, or trametinib for 72 h. Cell viability was determined by SRB assay. (C) Melanoma cell lines A375, A375/TR and A375/DR were treated with SHR8443, dabrafenib or trametinib for 2 h. Whole-cell lysates were analyzed by Western blotting using the indicated antibodies.