title: AVS-1357 inhibits melanogenesis via prolonged ERK activation.
abstract: In this study, we demonstrated that a derivative of imidazole, AVS-1357, is a novel skin-whitening compound. AVS-1357 was found to significantly inhibit melanin production in a dose-dependent manner; however, it did not directly inhibit tyrosinase. Furthermore, we found that AVS-1357 induced prolonged activation of extracellular signal-regulated kinase (ERK) and Akt, while it downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase. It has been reported that the activation of ERK and/or Akt is involved in melanogenesis. Therefore, we examined the effects of AVS-1357 on melanogenesis in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway) and/or LY294002 (a specific inhibitor of the Akt pathway). PD98059 dramatically increased melanogenesis, whereas LY294002 had no effect. Furthermore, PD98059 attenuated AVS-1357 induced ERK activation, as well as the downregulation of MITF and tyrosinase. These findings suggest that the effects of AVS-1357 occur via downregulation of MITF and tyrosinase, which is caused by AVS-1357-induced prolonged ERK activation. Taken together, our results indicate that AVS-1357 has the potential as a new skin whitening agent.
authors.affiliation: Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Seo-Hyoung
authors.initials: SH
authors.lastname: Park
authors.forename: Chong Hak
authors.initials: CH
authors.lastname: Chae
authors.forename: Kyoung-Chan
authors.initials: KC
authors.lastname: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000096:biosynthesis; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics
chemical_list: C544038:AVS-1357; D007093:Imidazoles; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014442:Monophenol Monooxygenase; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases