The receptor tyrosine kinase c-kit, activated by its ligand stem-cell factor (SCF), modulates diverse cellular processes, including cell proliferation, differentiation, and survival. ISCK03 is a cell-permeable inhibitor of SCF-mediated c-kit activation, completely blocking phosphorylation of c-kit in human melanoma cells at a concentration between 1 and 5 μM. These concentrations also prevent SCF-mediated downstream phosphorylation of p44/p42 ERK but does not prevent phosphorylation of p44/p42 ERK induced by hepatocyte growth factor. Oral administration of ISCK03 in mice induces hair depigmentation, whereas topical application decreases epidermal melanin in guinea pig skin darkened by UV irradiation. ISCK03 has also been used to elucidate the role of SCF/c-kit signaling in cell viability, radiation-induced angiogenesis, and melanocortin receptor action.
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