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There is an urgent need for better therapeutic options for advanced melanoma patients, particularly those without the BRAF V600E/K mutation. In melanoma cells, loss of TRIM16 expression is a marker of cell migration and metastasis, while the BRAF inhibitor, vemurafenib, induces melanoma cell growth arrest in a TRIM16-dependent manner. Here we identify a novel small molecule compound which sensitized BRAF wild-type melanoma cells to vemurafenib. High throughput, cell-based, chemical library screening identified a compound (C012) which significantly reduced melanoma cell viability, with limited toxicity for normal human fibroblasts. When combined with the BRAF V600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAF WT and 4 out of 5 BRAF V600E human melanoma cell lines (Combination Index: CI< 1), and, dramatically reduced colony forming ability. In …