Automated in vivo screen in zebrafish identifies clotrimazole as targeting a metabolic vulnerability in a melanoma model. (PubMed, Dev Biol)
We further tested two compounds for each of the 5 classes, and a farnesyltransferase inhibitor (Lonafarnib), that inhibits an essential post-translational modification of HRAS and suppresses the hyperpigmentation phenotype...Similar effects were observed with another hit of the same class, Miconazole. Furthermore, we show that the effects of clotrimazole are mediated by the inhibition of hexokinase activity, which is lethal to the abnormal metabolic profile of melanoma cells in vitro and in vivo. Thus, our study shows that the zebrafish can provide a phenotype-rich assay for fully automated screening approaches to identify drugs for synthetic lethal treatment in melanoma and suggest further testing of clotrimazole in combinatorial treatments.