In this study, we created A375LM5IF4g/Luc BRAF-mutant lung-seeking melanoma cells and demonstrated that the phyto-sesquiterpene lactone DET and its semi-synthetic derivative DETD-35 effectively suppress metastasis in an A375LM5IF4g/Luc lung metastatic melanoma xenograft mouse model with bioefficacy that is superior to the clinically used BRAF inhibitor PLX. Here, BRAF is linked to metastatic melanoma.