Protein Arginine Methyltransferase 6 (PRMT6) is a Type I PRMT enzyme that plays a role in the epigenetic regulation of gene expression by methylating histone and non-histone proteins. It is also involved in various cellular processes, including alternative splicing, DNA repair, and cell signaling. Furthermore, PRMT6 exerts multiple effects on cellular processes such as growth, migration, invasion, apoptosis, and drug resistance in various cancers, positioning it as a promising target for anti-tumor therapeutics. In this review, we initially provide an overview of the structure and biological functions of PRMT6, along with its association with cancer. Subsequently, we focus on recent progress in the design and development of modulators targeting PRMT6. This includes a comprehensive review of PRMT6 inhibitors (isoform-selective and non-selective), dual-target inhibitors based on PRMT6, PRMT6 covalent inhibitors, and PRMT6-targeting hydrophobic tagging (HyT) degraders, from the perspectives of rational design, pharmacodynamics, pharmacokinetics, and the clinical status of these modulators. Finally, we also provided the challenges and prospective directions for PRMT6 targeting drug discovery in cancer therapy.

中文翻译：

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PRMT6 调节剂在癌症治疗中的应用进展和出现的机会


蛋白精氨酸甲基转移酶 6 （PRMT6） 是一种 I 型 PRMT 酶，通过甲基化组蛋白和非组蛋白在基因表达的表观遗传调控中发挥作用。它还参与各种细胞过程，包括选择性剪接、DNA 修复和细胞信号传导。此外，PRMT6 对各种癌症的生长、迁移、侵袭、凋亡和耐药等细胞过程产生多种影响，使其成为抗肿瘤治疗的有前途的靶点。在这篇综述中，我们初步概述了 PRMT6 的结构和生物学功能，以及它与癌症的关联。随后，我们专注于靶向 PRMT6 的调节剂的设计和开发的最新进展。这包括从合理设计、药效学、药代动力学和这些调节剂的临床状态的角度对 PRMT6 抑制剂（亚型选择性和非选择性）、基于 PRMT6 的双靶点抑制剂、PRMT6 共价抑制剂和 PRMT6 靶向疏水标记 （HyT） 降解剂的全面评价。最后，我们还提供了癌症治疗中 PRMT6 靶向药物发现的挑战和前瞻性方向。