Small-Molecule Modulators Targeting Coactivator-Associated Arginine Methyltransferase 1 (CARM1) as Therapeutic Agents for Cancer Treatment: Current Medicinal Chemistry Insights and Emerging OpportunitiesClick to copy article linkArticle link copied!
- Shuqing LiShuqing LiKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Jiangxi Provincal Key Laboratory of Tissue Engineering, School of Pharmacy, Gannan Medical University, Ganzhou 341000, P. R. ChinaMore by Shuqing Li
- Wanyi PanWanyi PanKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Jiangxi Provincal Key Laboratory of Tissue Engineering, School of Pharmacy, Gannan Medical University, Ganzhou 341000, P. R. ChinaMore by Wanyi Pan
- Chengpeng TaoChengpeng TaoKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Jiangxi Provincal Key Laboratory of Tissue Engineering, School of Pharmacy, Gannan Medical University, Ganzhou 341000, P. R. ChinaMore by Chengpeng Tao
- Zhihao HuZhihao HuKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Jiangxi Provincal Key Laboratory of Tissue Engineering, School of Pharmacy, Gannan Medical University, Ganzhou 341000, P. R. ChinaMore by Zhihao Hu
- Binbin Cheng*Binbin Cheng*[email protected]School of Medicine, Hubei Polytechnic University, Huangshi 435003, ChinaMore by Binbin Cheng
- Jianjun Chen*Jianjun Chen*[email protected]School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 516000, ChinaMore by Jianjun Chen
- Xiaopeng Peng*Xiaopeng Peng*[email protected]Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Jiangxi Provincal Key Laboratory of Tissue Engineering, School of Pharmacy, Gannan Medical University, Ganzhou 341000, P. R. ChinaMore by Xiaopeng Peng
Abstract
Overexpression of coactivator associated arginine methyltransferase 1 (CARM1) is associated with various diseases including cancer. Therefore, CARM1 has emerged as an attractive therapeutic target and a drug response biomarker for anticancer drug discovery. However, the development of conventional CARM1 inhibitors has been hampered by their limited clinical efficacy, acquired resistance, and inability to inhibit nonenzymatic functions of CARM1. To overcome these challenges, new strategies such as isoform-selective inhibitors, dual-acting inhibitors, targeted protein degradation technology (e.g., PROTACs), and even activators, are essential to enhance the anticancer activity of CARM1 modulators. In this perspective, we first summarize the structure and biofunctions of CARM1 and its association with cancer. Next, we focus on the recent advances in CARM1 modulators, including isoform-selective CARM1 inhibitors, dual-target inhibitors, PROTAC degraders, and activators, from the perspectives of rational design, pharmacodynamics, pharmacokinetics, and clinical status. Finally, we discuss the challenges and future directions for CARM1-based drug discovery.
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