CARM1的研究进展及与乳腺癌的关系

组蛋白精氨酸甲基转移酶1（CARM1）,是蛋白质精氨酸甲基转移酶家族（PRMTs）的成员之一,也称为PRMT4。近年有文献报道CARM1是多种肿瘤相关转录因子的共激活因子,在多种肿瘤中表达异常,特别是在乳腺癌中。本文就CARM1在正常组织中的生物学功能、与雌激素依赖型乳腺癌发生发展的关系、在乳腺癌不同分子亚型中的作用及在肿瘤细胞中的功能进行研究和讨论,揭示其在乳腺癌中存在的生物学机制,对乳腺癌的治疗提出了可能性靶点。     

A patent review of arginine methyltransferase inhibitors (2010–2018)

Introduction: Protein arginine methyltransferases (PRMTs) are fundamental enzymes that specifically modify the arginine residues of versatile substrates in cells. The aberrant expression and abnormal enzymatic activity of PRMTs are associated with many human diseases, especially cancer. PRMTs are emerging as promising drug targets in both academia and industry.

Areas covered: This review summarizes the updated patented inhibitors targeting PRMTs from 2010 to 2018. The authors illustrate the chemical structures, molecular mechanism of action, pharmacological activities as well as the potential clinical application including combination therapy and biomarker-guided therapy. PRMT inhibitors in clinical trials are also highlighted. The authors provide a future perspective for further development of potent and selective PRMT inhibitors.

Expert opinion: Although a number of small molecule inhibitors of PRMTs with sufficient potency have been developed, the selectivity of most PRMT inhibitors remains to be improved. Hence, novel approaches such as allosteric regulation need to be further studied to identify PRMT inhibitors. So far, three PRMT inhibitors have entered clinical trials, including PRMT5 inhibitor GSK3326595 and JNJ-64619178 as well as PRMT1 inhibitor GSK3368715. PRMT inhibitors with novel mechanism of action and good drug-like properties may shed new light on drug research and development progress.