Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX.
Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX.
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新型合成吲哚酮衍生物作为靶向 p53-MDM2 和 p53-MDMX 的抗肿瘤药物的合成和生物学评价
DOI：
10.3390/molecules27123721
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发表时间：
2022-06-09
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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作者：
合成了一系列新型吲哚类化合物，并对它们与MDM2和MDMX的结合亲和力进行了评价。部分化合物表现出较强的MDM2和中等的MDMX活性。其中，化合物A13对MDM2和MDMX的亲和力最强，Ki分别为0.031和7.24μM。A13对HCT116、MCF7和A549的作用也最强，IC50值分别为6.17、11.21和12.49μM。Western印迹分析证实A13上调MDM2、MDMX和P53的表达。这些结果表明，A13是一种强大的P53-MDM2和P53-MDMX双重抑制因子，值得进一步研究。
A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a Ki of 0.031 and 7.24 μM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC50 values of 6.17, 11.21, and 12.49 μM, respectively. Western blot analysis confirmed that A13 upregulated the expression of MDM2, MDMX, and p53 by Western blot analysis. These results indicate that A13 is a potent dual p53-MDM2 and p53-MDMX inhibitor and deserves further investigation.
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DOI：
10.1186/s13058-021-01406-x
发表时间：
2021-03-04
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Pairawan S;Zhao M;Yuca E;Annis A;Evans K;Sutton D;Carvajal L;Ren JG;Santiago S;Guerlavais V;Akcakanat A;Tapia C;Yang F;Bose PSC;Zheng X;Dumbrava EI;Aivado M;Meric-Bernstam F
通讯作者：
Meric-Bernstam F
影响因子：
15
作者：
Ding, K;Lu, Y;Wang, SM
通讯作者：
Wang, SM
影响因子：
4.6
作者：
Mrkvova, Zuzana;Uldrijan, Stjepan;Slaninova, Iva
通讯作者：
Slaninova, Iva
影响因子：
4.8
作者：
Reed, Damon;Shen, Ying;Dyer, Michael A.
通讯作者：
Dyer, Michael A.
影响因子：
5.7
作者：
Koblish, HK;Zhao, SY;Maroney, AC
通讯作者：
Maroney, AC