ISCK03 is a cell-permeablec-Kit inhibitor with IC50 < < 2.5 μM in cell-free kinase assays and blocks SCF-inducedc-kit andErk phosphorylation (1 μM causes > 90% inhibition) without any effect on HGF-inducedErk phosphorylation in 501mel melanoma cells, it's a phenyl-imidazolosulfonamide compound.
C-kit belongs to the platelet-derived growth factor (PDGF) family of receptor tyrosine kinases (RTKs). It has been reported that the SCF(stem-cell factor)/c-kit signaling is related to melanocyte development and pigmentation. ISCK03 is a potent c-kit inhibitor and may be useful for treating hyperpigmented spots caused by effects on c-kit expression. In 501mel human melanoma cells, pretreatment with ISCK03 inhibited SCF-induced c-kit phosphorylation dose dependently. Furthermore, ISCK03 inhibited c-kit phosphorylation in vitro and SCF-induced c-kit phosphorylation in 501mel human melanoma cells in a dose-dependent manner. Complete inhibition was observed with 1 and 5 μM ISCK03. It also inhibited SCF-induced p44/42 ERK phosphorylation dose dependently (5.0, 1.0, 0.5, and 0.1 μM ISCK03 for 2 h). In mice, once-daily oral administration of ISCK03 (500, 250, or 125 mg/kg) had a dramatic dose-dependent effect on hair depigmentation. Moreover, 0.1% ISCK03 treatment abolished UV-induced hyperpigmentation in brownish guinea pigs. And the epidermal melanin was found to be decreased in the ISCK03-treated pigment spots[3].
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