Source:http://linkedlifedata.com/resource/pubmed/id/17658483
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2007-7-30
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| pubmed:abstractText |
It is well known that c-kit is related to pigmentation as well as to the oncology target protein. The objective of this study was to discover a skin-whitening agent that regulates c-kit activity. We have developed a high-throughput screening system using recombinant human c-kit protein. Approximately 10,000 synthetic compounds were screened for their effect on c-kit activity. Phenyl-imidazole sulfonamide derivatives showed inhibitory activity on c-kit phosphorylation in vitro. The effects of one derivative, [4-t-butylphenyl]-N-(4-imidazol-1-yl phenyl)sulfonamide (ISCK03), on stem-cell factor (SCF)/c-kit cellular signaling in 501mel human melanoma cells were examined further. Pretreatment of 501mel cells with ISCK03 inhibited SCF-induced c-kit phosphorylation dose dependently. ISCK03 also inhibited p44/42 ERK mitogen-activated protein kinase (MAPK) phosphorylation, which is known to be involved in SCF/c-kit downstream signaling. However ISCK03 did not inhibit hepatocyte growth factor (HGF)-induced phosphorylation of p44/42 ERK proteins. To determine the in vivo potency of ISCK03, it was orally administered to depilated C57BL/6 mice. Interestingly, oral administration of ISCK03 induced the dose-dependent depigmentation of newly regrown hair, and this was reversed with cessation of ISCK03 treatment. Finally, to investigate whether the inhibitory effect of ISCK03 on SCF/c-kit signaling abolished UV-induced pigmentation, ISCK03 was applied to UV-induced pigmented spots on brownish guinea pig skin. The topical application of ISCK03 promoted the depigmentation of UV-induced hyperpigmented spots. Fontana-Masson staining analysis showed epidermal melanin was diminished in spots treated with ISCK03. These results indicate that phenyl-imidazole sulfonamide derivatives are potent c-kit inhibitors and might be used as skin-whitening agents.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
1873-2968
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
1
|
| pubmed:volume |
74
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
780-6
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17658483-Animals,
pubmed-meshheading:17658483-Cell Line, Tumor,
pubmed-meshheading:17658483-Dose-Response Relationship, Drug,
pubmed-meshheading:17658483-Female,
pubmed-meshheading:17658483-Gene Expression Regulation,
pubmed-meshheading:17658483-Guinea Pigs,
pubmed-meshheading:17658483-Humans,
pubmed-meshheading:17658483-Hyperpigmentation,
pubmed-meshheading:17658483-Imidazoles,
pubmed-meshheading:17658483-Melanins,
pubmed-meshheading:17658483-Melanoma,
pubmed-meshheading:17658483-Mice,
pubmed-meshheading:17658483-Mice, Inbred C57BL,
pubmed-meshheading:17658483-Molecular Structure,
pubmed-meshheading:17658483-Phosphorylation,
pubmed-meshheading:17658483-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:17658483-Signal Transduction,
pubmed-meshheading:17658483-Sulfonamides
|
| pubmed:year |
2007
|
| pubmed:articleTitle |
[4-t-butylphenyl]-N-(4-imidazol-1-yl phenyl)sulfonamide (ISCK03) inhibits SCF/c-kit signaling in 501mel human melanoma cells and abolishes melanin production in mice and brownish guinea pigs.
|
| pubmed:affiliation |
Skin Research Institute, AMOREPACIFIC R&D Center, 314-1 Bora-dong, Giheung-gu, Yongin-si, 446-729, Republic of Korea.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|