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KI-328是一种针对KIT激酶的抑制剂,它对急性髓系白血病(AML)中常见的一些KIT突变体激酶具有选择性活性。KI-328在体外激酶实验中对KIT激酶表现出特异性,并能抑制野生型(Wt)和突变型KIT表达细胞的生长,但对D816V-KIT的活性较低。对几种有效KIT抑制剂对多种突变型KIT表达细胞生长抑制效果的比较分析显示,多激酶抑制剂对D816V-KIT的活性与其他突变型KIT相当;然而,热休克蛋白90(HSP90)抑制剂对D816V-KIT表现出显著的活性,而在不影响其他突变型KIT表达细胞生长的浓度下抑制D816V-KIT表达细胞的生长。这些结果表明,有效的KIT抑制剂对不同类型的KIT突变体激酶活性不同。因此,在临床开发中,KIT抑制剂需要验证对多种类型KIT突变体激酶的活性。

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KI-328 Chemical Structure

KI-328 Chemical Structure

CAS No. : 930089-25-1

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生物活性

KI-328 is a novel inhibitor targeting KIT kinase that has selective activity against some KIT mutant kinases commonly found in acute myeloid leukemia (AML). KI-328 showed specificity for KIT kinase in in vitro kinase assays and inhibited the growth of wild-type (Wt) and mutant KIT-expressing cells, but had lower activity against D816V-KIT. Comparative analysis of the inhibitory effects of several potent KIT inhibitors on the growth of multiple mutant KIT-expressing cells showed that the multi-kinase inhibitors had comparable activity against D816V-KIT as against other mutant KITs; however, heat shock protein 90 (HSP90) inhibitors showed significant activity against D816V-KIT, inhibiting the growth of D816V-KIT-expressing cells at concentrations that did not affect the growth of other mutant KIT-expressing cells. These results suggest that potent KIT inhibitors have different activities against different types of KIT mutant kinases. Therefore, in clinical development, KIT inhibitors need to validate their activity against multiple types of KIT mutant kinases.

分子量

471.51

Formula

C25H25N7O3

CAS 号
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产品名称:
KI-328
目录号:
HY-121708
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