Downregulation of melanogenesis: drug discovery and therapeutic options.
Melanin, primarily responsible in humans for hair, eye and skin pigmentation, is produced by melanocytes through a process called melanogenesis. However, the abnormal accumulation of melanin causes dermatological problems such as café-au-lait macules ephelides (freckles), solar lentigo (age spots) and melasma, as well as cancer and vitiligo. Hence the regulation of melanogenesis is very important for treating hyperpigmentary disorders. Numerous antimelanogenic agents that target tyrosinase activity and/or stability, melanosome maturation, transfer and trafficking, or melanogenesis-related signaling pathways have been developed. This article reviews recent advances in research and development of human tyrosinase and melanogenesis-related signaling pathway inhibitors. Attempts have been made to provide a complete description of the mechanism of action of inhibitors on various melanogenesis signaling pathways.
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany. Electronic address: thanigai@uni-bonn.de.
Thanigaimalai
T
Pillaiyar
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 34134, South Korea.
Manoj
M
Manickam
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 34134, South Korea.
Sang-Hun
SH
Jung
D000818:Animals; D001343:Autophagy; D000073840:Copper-Transporting ATPases / Q000378:metabolism; D015536:Down-Regulation; D055808:Drug Discovery; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D060449:Wnt Signaling Pathway
D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D009569:Nitric Oxide; D014442:Monophenol Monooxygenase; D020928:Mitogen-Activated Protein Kinases; D000073840:Copper-Transporting ATPases