Identification of a New Interesting BAG3 Modulator Able to Disrupt Cancer-Related Pathways.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-07-09 DOI:10.1002/cmdc.202500310

Dafne Ruggiero, Eleonora Boccia, Emis Ingenito, Vincenzo Vestuto, Gilda D'Urso, Alessandra Capuano, Agostino Casapullo, Stefania Terracciano, Giuseppe Bifulco, Gianluigi Lauro, Ines Bruno

引用次数: 0

Abstract

Continuing our research aimed at discovering new BAG3 modulators as attractive anticancer drug candidates, we performed a screening campaign on an in-house library, including compounds featuring a large variety of scaffolds. The obtained results induced us to focus on the triazole moiety and, following a stepwise structural refinement of the scaffold guided by biophysical assays and computational studies, we identified a very attractive compound (2) showing a tight interaction with BAG3 and displaying a significant cytotoxic activity. The discovery of compound 2, whose effects on apoptosis and proteostasis confirm the disruption of BAG3-related pathways, is particularly relevant given the limited number of BAG3 modulators reported so far. Moreover, our computational data highlight the potential to further explore the triazole scaffold for the development of more potent anticancer agents.

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一种能够破坏癌症相关通路的新的BAG3调节剂的鉴定

继续我们的研究旨在发现新的BAG3调节剂作为有吸引力的抗癌候选药物，我们在内部文库中进行了筛选活动，包括具有多种支架的化合物。获得的结果促使我们关注三唑部分，并在生物物理实验和计算研究的指导下逐步优化支架结构，我们发现了一个非常有吸引力的化合物(2)，它与BAG3紧密相互作用，并显示出显著的细胞毒性活性。化合物2的发现，其对细胞凋亡和蛋白酶抑制的作用证实了BAG3相关通路的破坏，鉴于迄今为止报道的BAG3调节剂数量有限，这一发现尤其重要。此外，我们的计算数据强调了进一步探索三唑支架的潜力，以开发更有效的抗癌药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

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