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ZFIN ID: ZDB-PUB-120514-8
Characterization of two novel small molecules targeting melanocyte development in zebrafish embryogenesis
Chen, L., Ren, X., Liang, F., Li, S., Zhong, H., and Lin, S.
Date: 2012
Source: Pigment cell & melanoma research   25(4): 446-453 (Journal)
Registered Authors: Lin, Shuo, Zhong, Hanbing
Keywords: melanocyte, zebrafish, chemical screen, melanoma, drug candidate
MeSH Terms:
  • Animals
  • Apoptosis/drug effects
  • Cell Differentiation/drug effects
  • Cell Line, Tumor
  • Cell Shape/drug effects
  • Cell Survival/drug effects
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/pathology
  • Embryonic Development/drug effects*
  • Humans
  • Melanocytes/drug effects
  • Melanocytes/metabolism
  • Melanocytes/pathology*
  • Melanoma/embryology
  • Melanoma/pathology
  • Mice
  • Pigmentation/drug effects
  • Small Molecule Libraries/chemistry
  • Small Molecule Libraries/pharmacology*
  • Time-Lapse Imaging
  • Zebrafish/embryology*
PubMed: 22574862 Full text @ Pigment Cell Melanoma Res.
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ABSTRACT

Melanocytes are pigment cells that are closely associated with many skin disorders, such as vitiligo, piebaldism, Waardenburg Syndrome, and the deadliest skin cancer, melanoma. Through studies of model organisms, the genetic regulatory network of melanocyte development during embryogenesis has been well established. This network also seems to be shared with adult melanocyte regeneration and melanoma formation. To identify chemical regulators of melanocyte development and homeostasis, we screened a small-molecule library of 6000 compounds using zebrafish embryos and identified five novel compounds that inhibited pigmentation. Here we report characterization of two compounds, 12G9 and 36E9, which disrupted melanocyte development. TUNEL assay indicated that these two compounds induced apoptosis of melanocytes. Furthermore, compound 12G9 specifically inhibited the viability of mammalian melanoma cells in vitro. These two compounds should be useful as chemical biology tools to study melanocytes and could serve as drug candidates against melanocyte-related diseases.

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