504. 1-(2,4-DIHYDROXYPHENYL)-3-(2,4-DIMETHOXY-3-METHYL-PHENYL)PROPANE, A NOVEL TYROSINASE INHIBITOR WITH STRONG DEPIGMENTING EFFECTS.

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Nesterov¹, A., Zhao¹, J., Minter², D., Hertel¹, C., Ma¹, W., Abeysinghe¹, P., Hong¹, M., and Jia¹, Q. ¹Unigen Pharmaceuticals, Inc.; 2660 Willamette Drive NE, Lacey, WA 98516, U.S.A.: and ²Chemistry Department, Texas Christian University; Fort Worth, TX 76129, USA. Chem. Pharm. Bull., 56(9) 1292-1296 (2008).

Summary:
This study by researchers at Unigen Pharmaceuticals and Texas Christian University demonstrated that MatTek's MelanoDerm in vitro human skin tissue equivalent is an excellent in vitro model for studying the efficacy and safety of novel human skin lightening compounds.

A series of diarylpropane compounds was isolated by screening a plant extract library for inhibitors of mushroom tyrosinase. The most potent compound, 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)- propane (UP302: CAS# 869743-37-3), was found in the medicinal plant Dianella ensifolia.

Synthetic and plant-derived versions of UP302 inhibited mushroom tyrosinase with similar potencies. UP302 inhibited mushroom tyrosinase with Ki=0.3 µM, in a competitive and reversible fashion. UP302 was 22 times more potent than Kojic acid in inhibiting murine tyrosinase, with IC₅₀ values of 12 and 273 µM respectively.

Experiments on mouse melanoma cells B16-F1 and on human primary melanocytes demonstrated that UP302 inhibits melanin formation with IC₅₀ values of 15 and 8 µM respectively. Long-term treatment of cultured melanocytes with up to 62 µM of UP302 revealed no detectable cytotoxicity.

In a reconstructed skin model (MelanoDerm) topical application of 0.1% UP302 resulted in significant skin lightening and decrease of melanin production without effects on cell viability, melanocyte morphology or overall tissue histology.

In conclusion, UP302 is a novel tyrosinase inhibitor that suppresses melanin production in both cultured melanocytes and reconstructed skin with high potency and without adverse side effects.

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MelanoDerm Data Sheet

MelanoDerm Technical Specifications

MelanoDerm Technical References

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Applications: Skin lightening/whitening

Keywords: MEL-300-B, Melanin content, MelanoDerm, Skin lightening, Skin whitening, Tyrosinase inhibitor

Materials Tested: 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane, 80% propylene glycol, Diarylpropane tyrosinase inhibitors, Kojic acid

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