Fig. 2

Blockade of FGFR/VEGFR receptors inhibits melanogenesis in a dose-dependent fashion. A Colormap representing the published IC50 values and inferred IC50 values from kinase inhibition studies for five separate multi-RTK inhibitors. B A premalignant mitfa-CRKL and MC-GFP zebrafish model of AM is utilized to test multi-RTK inhibitor effects against fin melanogenesis. C, D Phase contrast and GFP fluorescence imaging of multi-RTK treated zebrafish tails reveal that 3 µM Anlotinib, Cabozantinib, or Lenvatinib induce a marked decrease in fin melanogenesis. Each grey dot in D represents an individual zebrafish. The potency of each drug against VEGFRs or FGFRs is summarized underneath the x-axis: (+) potent against only one FGFR or VEGFR protein, (+ +) potent against all FGFR or VEGFR proteins, (-) not potent. E Tailfin melanocyte cell area quantification at different drug doses in mitfa-CRKL MC-GFP zebrafish. Similar doses of (F) Anlotinib and (G) Lenvatinib have intrinsic cytotoxic effects on cultured primary human melanocytes (see also Figure S1E). Drug abbreviations: Apa – Apatinib, Anlo – Anlotinib, Lenv – Lenvatinib, Cabo – Cabozantinib, Suni – Sunitinib