A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin.
Cell Rep
; 19(11): 2177-2184, 2017 06 13.
Article
in En
| MEDLINE
| ID: mdl-28614705
ABSTRACT
The presence of dark melanin (eumelanin) within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in "redhaired" Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK) has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Skin
/
Ultraviolet Rays
/
Melanins
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2017
Type:
Article
Affiliation country:
United States