We report the discovery, via a unique high-throughput screening strategy, of a novel bioactive anticancer compound: Thiol Alkylating Compound Inducing Massive Apoptosis (TACIMA)-218. We demonstrate that this molecule engenders apoptotic cell death in genetically diverse murine and human cancer cell lines, irrespective of their p53 status, while sparing normal cells. TACIMA-218 causes oxidative stress in the absence of protective antioxidants normally induced by Nuclear factor erythroid 2–related factor 2 activation. As such, TACIMA-218 represses RNA translation and triggers cell signaling cascade alterations in AKT, p38, and JNK pathways. In addition, TACIMA-218 manifests thiol-alkylating properties resulting in the disruption of redox homeostasis along with key metabolic pathways. When administered to immunocompetent animals as a monotherapy, TACIMA-218 has no apparent toxicity and induces complete regression of pre-established lymphoma and melanoma tumors. In sum, TACIMA-218 is a potent oxidative stress inducer capable of selective cancer cell targeting.

中文翻译：

---

TACIMA-218：一种具有选择性抗肿瘤活性的新型促氧化剂

我们通过独特的高通量筛选策略报告了一种新型生物活性抗癌化合物的发现：硫醇烷基化化合物诱导大规模细胞凋亡 (TACIMA)-218。我们证明，无论 p53 状态如何，该分子都会在基因多样的小鼠和人类癌细胞系中引起细胞凋亡，同时保留正常细胞。TACIMA-218 在缺乏通常由核因子红细胞 2 相关因子 2 激活诱导的保护性抗氧化剂的情况下引起氧化应激。因此，TACIMA-218 抑制 RNA 翻译并触发 AKT、p38 和 JNK 通路中的细胞信号级联改变。此外，TACIMA-218 表现出硫醇烷基化特性，导致氧化还原稳态和关键代谢途径的破坏。当作为单一疗法对具有免疫活性的动物给药时，TACIMA-218 没有明显的毒性，可诱导预先确定的淋巴瘤和黑色素瘤完全消退。总之，TACIMA-218 是一种有效的氧化应激诱导剂，能够选择性靶向癌细胞。