Discovery of new benzhydrol biscarbonate esters as potent and selective apoptosis inducers of human melanomas bearing the activated ERK pathway: SAR studies on an ERK MAPK signaling modulator, ACA-28
Discovery of new benzhydrol biscarbonate esters as potent and selective apoptosis inducers of human melanomas bearing the activated ERK pathway: SAR studies on an ERK MAPK signaling modulator, ACA-28
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DOI：
10.1016/j.bioorg.2020.104137
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发表时间：
2020-10-01
影响因子：
5.1
通讯作者：
Sugiura, Reiko
中科院分区：
文献类型：
--
作者：
Satoh, Ryosuke;Hamada, Naoya;Sugiura, Reiko
最近发现 ERK 信号调节剂 [ACA-28 (2a)] 通过诱导 ERK 依赖性细胞凋亡来优先杀死人类黑色素瘤细胞系，这一发现引起了抗癌治疗领域的极大兴趣。在第一个2a的SAR研究中，我们成功开发了候选物（2b，2c），它们都比2a诱导更有效和选择性的ERK活性黑色素瘤细胞凋亡，从而揭示了诱导ERK依赖性细胞凋亡的结构基础，并提出了这些候选物针对以黑色素瘤为代表的ERK依赖性癌症的治疗前景。
The recent discovery that an ERK signaling modulator [ACA-28 (2a)] preferentially kills human melanoma cell lines by inducing ERK-dependent apoptosis has generated significant interest in the field of anti-cancer therapy. In the first SAR study on 2a, here, we successfully developed candidates (2b, 2c) both of which induce more potent and selective apoptosis towards ERK-active melanoma cells than 2a, thus revealing the structural basis for inducing the ERK-dependent apoptosis and proposing the therapeutic prospect of these candidates against ERK-dependent cancers represented by melanoma.