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].
ISCK03 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Rat primary neurons
5 µM
1 hour
ISCK03, as a C-KIT specific inhibitor, was used to study the role of the Metrnl/C-KIT axis in neuronal ferroptosis. Results showed that ISCK03 treatment significantly reduced p-C-KIT expression and partially reversed the protective effects of r-Metrnl against neuronal ferroptosis.
CNS Neurosci Ther. 2025 Feb;31(2):e70286.
LS174T cells
30 µM
2.5 hours
Inhibited c-KIT phosphorylation, thereby inhibiting downstream p-ERK1/2 and p-ELK1 as well as CEA expression
Cancer Sci. 2021 Feb;112(2):655-667.
Mouse ovarian granulosa cells
5 µM
48 hours
Blocked the communication network between granulosa cells and oocytes, decreased pyruvate-free-promoted p-Akt and p-FOXO3a levels, but had no effect on pyruvate-free-promoted mTOR activity
Cell Death Dis. 2022 Jan 27;13(1):87.
K562 cells
10 µM or 20 µM
72 hours
ISCK03 treatment eliminated the increased survival of KD clones in the absence of serum.
Mol Cancer. 2015 Apr 19;14:90.
Mouse ovarian cells
2.5 µM
ISCK03 completely blocked TG-, CrCl3- and FeCl3-promoted p-Akt levels but had no effect on MnCl2- and ZnSO4-promoted p-Akt levels.
Theranostics. 2023 May 21;13(10):3131-3148.
ISCK03 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
Subarachnoid hemorrhage (SAH) model
Intracerebroventricular injection (i.c.v.)
2.5 mg/kg
Single administration 1 h before SAH induction
ISCK03, as a C-KIT specific inhibitor, was used to investigate the role of the Metrnl/C-KIT/AMPK/Nrf2 signaling pathway in neuronal ferroptosis after SAH. Results showed that ISCK03 treatment significantly reduced p-C-KIT expression and partially reversed the protective effects of r-Metrnl against neuronal ferroptosis.
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