An imbalance between protein aggregation and protein degradation may induce "stress" in the functionality of the endoplasmic reticulum. There are quality control mechanisms to minimize misfolding and to eliminate misfolded proteins before aggregation becomes lethal for the cell. Proper protein folding and maturation is one of the crucial functions of the endoplasmic reticulum. Chaperones of the endoplasmic reticulum and folding enzymes guarantee correct conformational maturation of emerging secretory proteins. HDAC6 is a masterpiece coordinating the cell response to protein aggregate formation. The balance between HDAC6 and its partner Valosin-containing protein/p97 determines the fate of polyubiquitinated misfolded proteins. WT161 is a terrific, selective, and bioavailable HDAC6 inhibitor. WT161 selectively inhibits HDAC6 and adequately increases levels of acetylated α-tubulin. This compound induces accumulation of acetylated tubulin and cytotoxicity in multiple myeloma (MM) cells. In this Journal, Dr. Sun et al. identified that WT161 suppresses the cell growth of osteosarcoma cells. This discovery opens the door to future chemotherapeutic regimens of this bone neoplasm.

中文翻译：

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HDAC6 抑制剂 WT161 对骨肉瘤具有抗肿瘤作用，并与 5-FU 协同作用。

蛋白质聚集和蛋白质降解之间的不平衡可能会导致内质网功能的“压力”。有质量控制机制可以最大限度地减少错误折叠并在聚集对细胞致命之前消除错误折叠的蛋白质。适当的蛋白质折叠和成熟是内质网的关键功能之一。内质网和折叠酶的分子伴侣保证新兴分泌蛋白的正确构象成熟。HDAC6 是协调细胞对蛋白质聚集体形成的反应的杰作。HDAC6 与其伙伴含 Valosin 蛋白/p97 之间的平衡决定了多泛素化错误折叠蛋白的命运。WT161 是一种极好的、选择性和生物可利用的 HDAC6 抑制剂。WT161 选择性抑制 HDAC6 并充分增加乙酰化 α-微管蛋白的水平。该化合物诱导多发性骨髓瘤 (MM) 细胞中乙酰化微管蛋白的积累和细胞毒性。在本期刊中，Sun 博士等人。确定 WT161 抑制骨肉瘤细胞的细胞生长。这一发现为未来这种骨肿瘤的化疗方案打开了大门。