Methods and compositions that affect melanogenesis
AssigneeNew York University
InventorsSeth J. Orlow, Andrea Hall, Prashiela Manga
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Abstract
The invention provides methods of screening for compounds that affect melanogenesis and the function of P protein in organisms, cells, or cell-free systems. The invention further relates to pharmacologic and cosmetic uses of methods of inhibiting melanogenesis, methods of activating melanogenesis, and compounds and pharmacologic compositions useful for the inhibition or activation of melanogenesis and, therefore, for lightening or darkening the pigmentation of cells and tissue, i.e., skin.
Claims77
A method of screening for compounds that inhibit melanogenesis, the method comprising:
- treating cells expressing a tyrosinase-encoding gene with a test compound, and determining the cellular localization of tyrosinase in the presence of the test compound;
- wherein a change in the cellular localization of tyrosinase in the presence of the test compound as compared to in the absence of the test compound indicates that the test compound is a candidate for a compound that inhibits melanogenesis.
A method of screening for compounds that increase melanogenesis comprising:
- treating cells expressing a tyrosinase-encoding gene with a test compound, and determining the amount of tyrosinase secreted by the cells in the presence of the test compound;
- wherein a decrease in the amount of tyrosinase secreted by the cells in the presence of the test compound as compared to in the absence of the test compound indicates that the test compound is a candidate for a compound that increases melanogenesis.
A method of screening for compounds that affect the function of P protein, the method comprising:
- contacting a system with a test compound, the system comprising P protein and tyrosinase;
- and identifying those test compounds that affect tyrosinase activity in the system in a P protein-dependent manner.
A method of screening for compounds that affect the function of P protein, the method comprising:
- using a primary screening method to preliminarily determine whether a test compound may affect P protein function;
- and using one or more secondary screening methods to determine whether the test compound affects P protein function.
A method of screening for compounds that affect the function of P protein, the method comprising:
- modeling a compound that affects the function of the P protein;
- making chemical analogs of the compound;
- and assaying the chemical analogs for their effect on the function of P protein.
A method of decreasing melanin production in a melanocyte, comprising contacting the melanocyte with an effective amount of a compound that effects an alteration in late endosomal/lysosomal trafficking in the melanocyte, wherein the alteration in late endosomal/lysosomal trafficking results in a decrease in melanin product
A method of reducing skin pigmentation, comprising contacting skin with a pharmaceutically effective amount of a compound that effects an alteration in late endosomal/lysosomal trafficking, wherein an alteration in late endosomal/lysosomal trafficking results in a reduction of skin pigmentation.
A method of activating melanogenesis comprising contacting a melanocyte with diminished or absent P protein activity with a pharmaceutically effective amount of a compound that inhibits ATPase, whereby the inhibition of ATPase results in an activation of melanogenesis in the melanocyte with diminished or absent P protein activity.
A method of treating tyrosinase-positive, oculocutaneous albinism in an individual in need thereof, the method comprising contacting skin of the individual with a pharmaceutically effective amount of a compound that inhibits ATPase, whereby the inhibition of ATPase results in an activation of melanogenesis in the individual.
Dependencies are inferred from the claim text.