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INDUCERS OF GAMMA GLOBIN GENE EXPRESSION AND SCREENING ASSAYS THEREFOR
INDUCERS OF GAMMA GLOBIN GENE EXPRESSION AND SCREENING ASSAYS THEREFOR
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机译:γ球蛋白基因表达的诱导物及其筛选评估
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摘要
Methods for stimulating gamma globin gene expression in a mammalian cellcomprising contacting the cell with a compound selected from valeric acid andcertain isomers, derivatives or salts thereof, including isovaleric acid, 4-pentynoic acid and methylthioacetic acid, or an inhibitor of a short chainfatty acyl CoA dehydrogenase, or an activator of protein kinase C aredisclosed. The methods of the invention are particularly useful forameliorating .beta.-globin disorders, such as sickle cell anemia or .beta.-thalassemia. The method of the invention can also be used to prevent orameliorate malaria in a mammal. The compounds of the invention can also beused to stimulate differentiation of a cell. Pharmaceutical compositions ofthe acive compounds of the invention are also disclosed. Screening assays foridentifying agents that stimulate gamma globin gene expression in an erythroidcell, stimulate cell differentiation or stimulate transport of a short chainfatty acid, or derivative or salt thereof, into cells are also disclosed.
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