A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin

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A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin

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Title: A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin
Author: Mujahid, Nisma; Liang, Yanke; Murakami, Ryo; Choi, Hwan Geun; Dobry, Allison S.; Wang, Jinhua; Suita, Yusuke; Weng, Qing Yu; Allouche, Jennifer; Kemeny, Lajos V.; Hermann, Andrea L.; Roider, Elisabeth M.; Gray, Nathanael S.; Fisher, David E.

Note: Order does not necessarily reflect citation order of authors.

Citation: Mujahid, N., Y. Liang, R. Murakami, H. G. Choi, A. S. Dobry, J. Wang, Y. Suita, et al. 2017. “A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin.” Cell reports 19 (11): 2177-2184. doi:10.1016/j.celrep.2017.05.042. http://dx.doi.org/10.1016/j.celrep.2017.05.042.
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Abstract: SUMMARY 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.
Published Version: doi:10.1016/j.celrep.2017.05.042
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549921/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34375297
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