In a recent study in , exploiting strain release by malolactone-based electrophiles designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog (K-Ras)-G12D variant, which is highly prevalent in pancreatic cancer. The compound drastically inhibited oncogenic signaling and tumor growth in preclinical K-Ras-G12D-mutant pancreatic cancer models, expanding treatment potential beyond K-Ras-G12C-targeted therapies.

中文翻译：

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马洛内酯的攻击：K-Ras-G12D 的致命弱点


在最近的一项研究中，利用基于丙二酸内酯的亲电子试剂释放菌株，设计了一种一流的共价抑制剂，该抑制剂针对克尔斯滕大鼠肉瘤病毒致癌基因同源物 (K-Ras)-G12D 变体中难以捉摸的天冬氨酸，该变体在胰腺癌。该化合物在临床前 K-Ras-G12D 突变胰腺癌模型中显着抑制致癌信号传导和肿瘤生长，从而将治疗潜力扩展到 K-Ras-G12C 靶向疗法之外。