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Inducers of gamma globin gene expression and screening assays therefor

机译:γ珠蛋白基因表达的诱导物及其筛选测定

摘要

Methods for stimulating gamma globin gene expression in a mammalian cell comprising contacting the cell with a compound selected from valeric acid and certain isomers, derivatives or salts thereof, including isovaleric acid, 4-pentynoic acid and methylthioacetic acid, or an inhibitor of a short chain fatty acyl CoA dehydrogenase, or an activator of protein kinase C are disclosed. The methods of the invention are particularly useful for ameliorating -globin disorders, such as sickle cell anemia or -thalassemia. The method of the invention can also be used to prevent or ameliorate malaria in a mammal. The compounds of the invention can also be used to stimulate differentiation of a cell. Pharmaceutical compositions of the active compounds of the invention are also disclosed. Screening assays for identifying agents that stimulate gamma globin gene expression in an erythroid cell, stimulate cell differentiation or stimulate transport of a short chain fatty acid, or derivative or salt thereof, into cells are also disclosed.
机译:刺激哺乳动物细胞中γ珠蛋白基因表达的方法,该方法包括使细胞与选自戊酸及其某些异构体,衍生物或盐的化合物接触,所述化合物包括异戊酸,4-戊酸和甲硫基乙酸,或短链抑制剂公开了脂肪酰基CoA脱氢酶或蛋白激酶C的活化剂。本发明的方法对于减轻-球蛋白疾病例如镰状细胞性贫血或地中海贫血特别有用。本发明的方法还可用于预防或减轻哺乳动物中的疟疾。本发明的化合物也可以用于刺激细胞分化。还公开了本发明的活性化合物的药物组合物。还公开了用于鉴定刺激红系细胞中的γ球蛋白基因表达,刺激细胞分化或刺激短链脂肪酸或其衍生物或盐进入细胞的试剂的筛选测定法。

著录项

  • 公开/公告号US5700640A

    专利类型

  • 公开/公告日1997-12-23

    原文格式PDF

  • 申请/专利权人 BASF AKTIENGESELLSCHAFT;

    申请/专利号US19940308461

  • 发明设计人 JEFFREY W. VOSS;CONNIE CARON;

    申请日1994-09-16

  • 分类号C12Q1/68;

  • 国家 US

  • 入库时间 2022-08-22 02:40:40

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