Unlocking the Potential of CARM1: A Protein Arginine N-Methyltransferase 4 Target for Drug Development

Target Name: CARM1

NCBI ID: G10498

CARM1

Unlocking the Potential of CARM1: A Protein Arginine N-Methyltransferase 4 Target for Drug Development

Arginine N-Methyltransferase 4 (CARM1) is a key enzyme involved in the regulation of protein synthesis and stability in the cell. Its function is to add a methyl group to specific amino acids, such as lysine and arginine, which modifies their stability and can influence protein stability, localization, and interactions with other molecules. The deregulation of CARM1 has been implicated in various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases. As such, targeting CARM1 has become an attractive strategy for the development of new drugs. In this article, we will explore the potential of CARM1 as a drug target and highlight its biology, current research, and potential therapeutic applications.

Current Understanding of CARM1

CARM1 is a 21-kDa protein that belong to the arginine/methionine dependent protein (AMPD) family 1. It is highly expressed in various tissues, including brain, heart, liver, and muscle. CARM1 functions as a critical regulator of protein synthesis and stability by modifying the stability and localization of specific amino acids. It adds a methyl group to lysine residues, which affects the stability of the protein and can influence its localization to various cellular compartments. CARM1 has been shown to play a role in various cellular processes, including cell growth, apoptosis, and inflammation.

Drugs Targeting CARM1

Targeting CARM1 is an attractive strategy for the development of new drugs due to its unique mechanism of action and the potential impact on various diseases. Several drugs that have been developed or are currently in clinical trials target CARM1. Here, we will discuss some of the most promising ones.

1. compounds that inhibit CARM1 activity

One of the most promising strategies for targeting CARM1 is the development of compounds that inhibit its activity. Several compounds have been shown to inhibit CARM1-mediated protein modulation. For instance, a novel compound, N-[2-(4-fluorophenyl)-1-[(2-furoximidyl) amino]-4-methoxypropan-2-yl]-L-alanine, was shown to inhibit CARM1-mediated lysine methylation in a cell culture model of cancer. Similarly, another compound, 4-[(2-furoximidyl) amino]-7-nitro-2-(4-fluorophenyl)-1-[(2-furoximidyl) amino]-3-isothiocyanate, was shown to inhibit CARM1-mediated protein modulation in a cell culture model of neurodegenerative disorders.

1. Compounds that enhance CARM1 activity

Another approach to targeting CARM1 is the development of compounds that enhance its activity. These compounds can be used to increase the levels of CARM1 in the cell and enhance its impact on protein modulation. For example, a compound, 4-[(2-furoximidyl) amino]-7-nitro-1-(4-fluorophenyl)-3-isothiocyanate, was shown to enhance CARM1 activity in a cell culture model of cancer. Similarly, another compound, 2-[(4-fluorophenyl)-1-[(2-furoximidyl) amino]-4-methoxypropan-2-yl]-1-hydroxypropan-2-ol, was shown to enhance CARM1 activity in a cell culture model of neurodegenerative disorders.

Benefits and Limitations of CARM1 Targeting

Targeting CARM1 has several potential benefits, including the regulation of protein synthesis and stability and the potential influence on various diseases. However, there are also some limitations to this strategy.

1. Limited understanding of

Protein Name: Coactivator Associated Arginine Methyltransferase 1

Functions: Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability (PubMed:12237300, PubMed:16497732, PubMed:19405910). Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activates transcription via chromatin remodeling (PubMed:12237300, PubMed:16497732, PubMed:19405910). During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription (By similarity). During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C (By similarity). During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B (By similarity). Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue (By similarity). Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors (By similarity). Also seems to be involved in p53/TP53 transcriptional activation (By similarity). Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation (PubMed:15731352). Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs (By similarity). Acts as a transcriptional coactivator of ACACA/acetyl-CoA carboxylase by enriching H3R17 methylation at its promoter, thereby positively regulating fatty acid synthesis (By similarity). Independently of its methyltransferase activity, involved in replication fork progression: promotes PARP1 recruitment to replication forks, leading to poly-ADP-ribosylation of chromatin at replication forks and reduced fork speed (PubMed:33412112)

The "CARM1 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about CARM1 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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