Satoh Ryosuke, Hamada Naoya, Yamada Ami, Kanda Yuki, Ishikawa Fumihiro, Takasaki Teruaki, Tanabe Genzoh, Sugiura Reiko
Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan.
Laboratory of Organic Chemistry, Faculty of Pharmacy, Kindai University, Kowakae 3-4-1, Higashiosaka City, Osaka 577-8502, Japan.
Bioorg Chem. 2020 Oct;103:104137. doi: 10.1016/j.bioorg.2020.104137. Epub 2020 Jul 25.
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.
最近发现一种ERK信号调节剂[ACA - 28 (2a)]通过诱导ERK依赖性凋亡优先杀死人黑色素瘤细胞系，这在抗癌治疗领域引起了极大关注。在此，在对2a的首次构效关系（SAR）研究中，我们成功开发了候选物（2b、2c），这两种候选物对ERK活性黑色素瘤细胞诱导的凋亡比2a更有效且更具选择性，从而揭示了诱导ERK依赖性凋亡的结构基础，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。
