METHOD OF SCREENING ABC PROTEIN PROMOTER/INHIBITOR

摘要

Screening (M1) substances promoting or inhibiting the active transport of an ABC (ATP-binding cassette) protein involves: (a) constructing transformed yeast cells having the ABC protein expressed on the cell membrane, (b) culturing the transformant yeast with a test substance, and (c) comparing the growth level with that observed in a control. Screening (M1) substances promoting or inhibiting the active transport of an ABC (ATP-binding cassette) protein involves: (a) transferring an ABC protein gene into highly drug-sensitive yeast cells to construct transformed yeast cells having the ABC protein expressed on the cell membrane; (b) culturing the transformant yeast cells in the presence of a substance which is transported outside the cells by the ABC protein occurring in the cell membrane and has cytotoxicity on the yeast cells, with a test substance; and (c) comparing the growth level with that observed in a control. Independent claims are also included for: (1) screening substance with low cytotoxicity and promotion or inhibition on the active transport of an ABC protein comprising the steps (a), (b) and (c); and also assaying the proliferation or inhibitory effect on highly drug sensitive yeast cells that do not express the ABC protein; (2) transformant yeast cells that express ABC protein on the cell membrane obtained by transferring the ABC protein gene into highly drug sensitive yeast cells; (3) compounds screened; (4) compounds containing a partial structure of formula (I), their reduced derivatives or esters, with molecular weight of 1193.7, which can inhibit the transport of an ABC protein; (5) ABC protein inhibitors containing compounds of formula A-R4>-R5> (II); and (6) similar ABC protein inhibitors containing compounds of formula (XII), their ethers or esters, or compounds of formula (XIII), or their ethers or esters. [Image] A : a group of formula (III); R4>a group of formula (IV) or (V); R5>group of formula D-E-F1>-G-Z; R1>H or 1-6C lower alkyl; R : H or OH; m : 3-5; n : 4-6; p : 1-2; X : O, S or NH; D : a group of (VI); s : 4-6; E : a group of (VII); t : 2-4; F1 : group of formula (VIII); R2>H, OH or 1-6C lower alkyl; u : 1 or 2; G : a group of formula (IX); R3>1-6C lower alkyl; v : 3-5; w : 1-3; Z : substituents; R6>-[CH(OH)]5-; R7>-[CH(CH3)CH(OH)]2-; R8>-CH(OH)-CH2-CH(OH)-; R1>0>n-octyl; R9>n-nonyl; and R1>1>-CH2-CH(OH)-. ACTIVITY : Cytostatic. MECHANISM OF ACTION : None given in source material.