Patent DE-102005056890-A1 (DE)
Title: Method for evaluating effectiveness of aryl-hydrocarbon receptor agonist and antagonist comprises exposing a cell to the agonist and antagonist, treating exposed cell with UV-B radiation and determining induction of AhR-inducible gene
Inventor: KRUTMANN JEAN
IPC: A61Q19/00
Filed: 2005-11-28
Abstract: Method for evaluating the effectiveness of aryl-hydrocarbon receptor (AhR) agonist and AhR-antagonist comprises: (i) exposing a cell of an ex-vivo or in-vitro melanocyte and/or keratinocyte cell culture or of an in-vitro skin model to a possible AhR agonist and/or AhR antagonist; (ii) treating the exposed cell with UV-B radiation or with an AhR agonist, if the cell in step (i) is exposed to a possible AhR antagonist, and (iii) determining the induction of the AhR-inducible gene, preferably of CYP1A1. Independent claims are included for: (1) a method for screening of a substance library on AhR agonist and/or antagonist, comprising providing a sample of each of the substances of the substance library; carrying out the steps (i)-(iii) with the collected samples, (iv) exposing an untreated cell from (step (i)) to 2-methoxy-4-[7-methoxy-3-methyl-5-((E)-propenyl)-2,3-dihydro-benzofuran-2-yl]-phenol, (v) treating the exposed cell with UV-B radiation, (vi) determining the induction of the AhR-inducible gene determined in step (iii), and (vii) comparing the gene induction determined in step (iii) and (vi), where the exposed cells of step (ii) and optionally in step (v) are treated with a polycyclic aromatic hydrocarbon and preferably with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); selecting those substances as AhR antagonists, in whose samples the induction of an AhR-inducible gene is reduced by a pre-selected measure, and/or selecting those substances as AhR agonist, in whose samples the expression of an AhR-inducible gene is increased by a preselected measure; (2) a method for the manufacture of skin protection preparation comprising: mixing the AhR agonist and/or -antagonist with a cosmetically and/or pharmaceutically compatible carrier, so that the concentration of the AhR agonist and/or -antagonist in the mixture is at least double in amount compared to the minimum concentration necessary for reducing the induction of the AhR-induced gene, where the minimum concentration is determined by the above method; (3) a benzofuran compound of formula (II); (4) a device for accomplishing a high-throughput screening process comprising: a sample holder for at least 96 samples, luminescent agents for exposing the samples to UV-B radiation, a tool for determining the induction of an AhR-inducible gene in one of the 96 samples, and evaluation tool for indicating the induction of the AhR-inducible gene; (5) a method for evaluating the effectiveness of a skin-bleach and/or -tan, comprising: (a) exposing a cell to a possible skin-bleach and/or -tan; (b) determining the mass of the melanin formation of the cell treated in (a); (c) exposing an untreated cell from (a) to 2-methoxy-4-[7-methoxy-3-methyl-5-((E)-propenyl)-2,3-dihydro-benzofuran-2-yl]-phenol, if the effectiveness of the skin bleach has to be evaluated, and exposing the untreated cell to formylindolo(3,2b)carbazole, if the effectiveness of a skin tan is to be evaluated, (d) determining the mass of the melanin formation of the cell treated in (c); (e) comparing the bleaching of the skin determined in (b) and (d); (6) a method for manufacturing of a skin bleaching preparation, comprising mixing skin bleach with a cosmetically- and/or pharmaceutically-compatible carrier, so that the concentration of the skin bleach in the mixture is at least double in amount compared to the minimum concentration necessary for bleaching of the skin, where the minimum concentration is determined by the above method; (7) a composition comprising (II) and a pharmaceutically- and/or cosmetically-compatible carrier, for reducing or preventing a translocation of AhR into a cell core, UV-B induced- or -inducible gene expression, gene expression that is induced or inducible by a polycyclic aromatic hydrocarbon, preferably TCDD, and/or UV-B induced or -inducible skin damages, preferably skin cancer, skin aging, skin inflammations and sun burns; and (8) a medicament comprising (II). R 1>-R 9>H (preferred), OH, 1-12C alkoxy, 1-12C alkyl or 2-12C alkenyl groups; n : 0 or 1; Y 1>O, -CH- or -C(CH 3)-; X : O or methylene; and broken line : either a double bond or two hydrogen atoms. [Image] ACTIVITY : Dermatological; Cytostatic; Antiinflammatory; Vulnerary. MECHANISM OF ACTION : Aryl-hydrocarbon receptor antagonist.