Page 28 - A. Aging
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[A. Aging-16]
Identification of HPOB as a potent inhibitior of tyrosinase
Hyerim Song¹, Yun Jeong Hwang¹, Jae Won Ha¹, Yong Chool Boo¹˙*
¹Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University, Daegu
41944, Korea
The aim of this study was to identify novel antimelanogenic drugs from a drug library. Of 141 drugs tested, K8 (4-
((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-phenyl-benzeneacetamide; HPOB) was found to effectively inhibit
the α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis in B16-F10 murine melanoma cells
without accompanying cytotoxicity. Additional experiments showed that K8 did not significantly reduce the mRNA
and protein level of tyrosinase (TYR) or microphthalmia-associated transcription factor (MITF) in cells, but it potently
inhibited the catalytic activity TYR in vitro (IC50, 1.1-1.5 µM) as compared to β-arbutin (IC50, 500–700 µM) or kojic
acid (IC50, 63 µM). K8 showed copper chelating activity similar to kojic acid. Therefore, these data suggest that K8
inhibits cellular melanin synthesis not by downregulation of TYR protein expression, but by direct inhibition of TYR
catalytic activity through copper chelation. This study identified K8 as a potent inhibitor of cellular melanin synthesis,
which may be useful for the treatment of hyperpigmentation disorders.
