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A novel adamantyl benzylbenzamide derivative, AP 736, suppresses melanogenesis through the inhibition of c AMP ‐ PKA ‐ CREB ‐activated microphthalmia‐associated transcription factor and tyrosinase expression
Author(s) -
Lee Chang Seok,
Jang WonHee,
Park Miyoung,
Jung Kyoungmi,
Baek Heung Soo,
Joo Yung Hyup,
Park YoungHo,
Lim KyungMin
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12248
Subject(s) - tyrosinase , creb , microphthalmia associated transcription factor , melanin , chemistry , cyclic amp response element binding protein , protein kinase a , transcription factor , microbiology and biotechnology , skin hyperpigmentation , downregulation and upregulation , biochemistry , hyperpigmentation , biology , enzyme , gene
Melanogenesis is essential for the protection of skin against UV , but excessive production of melanin causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we found that a tyrosinase inhibitor, AP 736 (5‐adamantan‐1‐yl‐ N ‐(2,4‐dihydroxy‐benzyl)‐2,4‐dimethoxy‐benzamide) potently suppresses tyrosinase expression, and the mechanism underlying was elucidated. AP 736 attenuated the melanin production induced by diverse melanogenic stimuli in murine and human melanocytes. It suppressed the expression of key melanogenic enzymes; tyrosinase, tyrosinase‐related protein‐1 and tyrosinase‐related protein‐2. The expression of microphthalmia‐associated transcription factor ( M i TF ), a major promoter of melanogenesis was also decreased. AP 736 inhibited the activation of c AMP response element‐binding protein ( CREB ) and phosphokinase A ( PKA ), and c AMP elevation, reflecting that c AMP ‐ PKA ‐ CREB signalling axis was suppressed, resulting in the downregulation of M i TF and tyrosinase. Along with the previously reported tyrosinase inhibitory activity, the suppression of c AMP ‐PKA‐ CREB ‐mediated M i TF and tyrosinase expression by AP 736 may be efficient for the treatment for hyperpigmentation.