General description
一种F508del-CFTR校正剂。
KM11060 is a novel corrector of the F508del-CFTR trafficking defect. Target: CFTR in vitro: Small-molecule correctors such as KM11060 may serve as useful pharmacological tools in studies of the F508del-CFTR processing defect and in the development of cystic fibrosis therapeutics. KM11060 rescues F508del-CFTR trafficking in cultured cells and native epithelial tissues. KM11060 partially corrects F508del-CFTR processing and increases surface expression to 75% of that observed in cells incubated at low temperature. Up to 50% of the F508del-CFTR in cells treated with KM11060 was complex-glycosylated, indicating passage through the Golgi. KM11060 as a promising compound for further development of CF therapeutics.
In vivo: In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1) or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice.
KM11060是F508del-CFTR交易缺陷的新型校正器。目标：体外CFTR：KM11060等小分子校正剂可作为F508del-CFTR加工缺陷研究和囊性纤维化治疗药物开发中的有用药理工具。 KM11060挽救了F508del-CFTR在培养细胞和天然上皮组织中的运输。 KM11060部分纠正F508del-CFTR加工，并将表面表达提高到在低温下孵育的细胞中观察到的表面表达的75％。用KM11060处理的细胞中，高达50％的F508del-CFTR被复合糖基化，表明其通过了高尔基体。 KM11060是用于CF治疗药物的有前途的化合物。
体内：在LPS诱导的急性肺部炎症中，对PSGL-1（P-选择素糖蛋白配体-1）或P-选择素的阻滞，WEB2086对PAF的拮抗作用或KM11060对CFTR突变运输的纠正可显着增加血浆脂蛋白A4与野生型小鼠有关的F508del中的水平。
安全信息
