Kim, Dong-Seok Jeong, Yun-Mi Park, Ik-Kyu Hahn, Hoh-Gyu Lee, Hyun-Kyung Kwon, Sun-Bang Jeong, Ji Hoon Yang, Sung Jun Sohn, Uy Dong Park, Kyoung-Chan 2024-01-21T01:35:52Z 2024-01-21T01:35:52Z 2021-09-04 2007-01 0918-6158 https://pubs.kist.re.kr/handle/201004/134786 During our on-going attempts to develop a new skin-whitening agent, we identified a novel candidate compound KEG22394, a 2-imino-1,3-thiazoline derivative. Our data show that KHG22394 significantly inhibits melanin production in a dose-dependent manner, but that it does not directly inhibit tyrosinase, the rate limiting melanogenic enzyme. It has been reported that the activation of extracellular signal-regulated kinase (ERK) reduces melanin synthesis by downregulating microphthalmia-associated transcription factor (Mitf). Thus, we examined the effects of KHG22394 on the ERK pathway and found that it induced ERK and 90 kDa ribosomal S6 kinase (RSK-1) activation. Moreover, alpha-melanocyte-stimulating hormone (alpha-MSH) is known to increase melanin biosynthesis by increasing tyrosinase production, and here, we found that tx-MSH-induced Mitf and tyrosinase increases were inhibited in B16 melanoma cells treated with KHG22394. These findings suggest that the hypopigmentary effect of KHG22394 results from the downregulation of Mitf and subsequently of tyrosinase, although KHG22394 did not inhibit tyrosinase activity directly. Our findings indicate that 2-imino-1,3-thiazoline derivatives are potential skin whitening agents. English PHARMACEUTICAL SOC JAPAN MICROPHTHALMIA GENE-PRODUCT TRANSCRIPTION FACTOR MITF ACTIVATED PROTEIN-KINASE STIMULATING HORMONE FUNCTIONAL-ANALYSIS MAGNAPORTHE-GRISEA HUMAN MELANOCYTES ERK ACTIVATION CYCLIC-AMP IN-VITRO A new 2-imino-1,3-thiazoline derivative, KHG22394, inhibits melanin synthesis in mouse B16 melanoma cells Article 10.1248/bpb.30.180 1 BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.30, no.1, pp.180 - 183 BIOLOGICAL & PHARMACEUTICAL BULLETIN 30 1 180 183 scie scopus 000243960400035 2-s2.0-33846088970 Pharmacology & Pharmacy Pharmacology & Pharmacy Article MICROPHTHALMIA GENE-PRODUCT TRANSCRIPTION FACTOR MITF ACTIVATED PROTEIN-KINASE STIMULATING HORMONE FUNCTIONAL-ANALYSIS MAGNAPORTHE-GRISEA HUMAN MELANOCYTES ERK ACTIVATION CYCLIC-AMP IN-VITRO KHG22394 melanogenesis tyrosinase microphthalmia-associated transcription factor (Mitf)