PLX8394 is a selective inhibitor of the BRAF V600E kinase, designed to target cancers driven by this specific mutation. It is primarily investigated for the treatment of solid tumors, including melanoma, non-small cell lung cancer, and colorectal cancer, where the BRAF V600E mutation is prevalent. Unlike earlier BRAF inhibitors, PLX8394 does not induce paradoxical activation of the MAPK pathway in wild-type BRAF cells, reducing the risk of secondary skin tumors and other side effects. This makes it a promising option for long-term therapy. It has shown activity in both treatment-naïve and previously treated patients, including those who developed resistance to first-generation BRAF inhibitors. Additionally, PLX8394 crosses the blood-brain barrier effectively, offering potential in managing brain metastases. Clinical development is ongoing to evaluate its efficacy as a monotherapy and in combination with MEK inhibitors.