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coactivator associated arginine methyltransferase 1

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Target not currently curated in GtoImmuPdb

Target id: 1255

Nomenclature: coactivator associated arginine methyltransferase 1

Abbreviated Name: PRMT4

Family: 2.1.1.- Protein arginine N-methyltransferases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 608 19p13.2 CARM1 coactivator associated arginine methyltransferase 1
Mouse - 608 9 A3 Carm1 coactivator-associated arginine methyltransferase 1
Rat - 651 8q13 Carm1 coactivator-associated arginine methyltransferase 1
Previous and Unofficial Names Click here for help
Histone-arginine methyltransferase CARM1 | protein arginine N-methyltransferase 4
Database Links Click here for help
Alphafold Q86X55 (Hs), Q9WVG6 (Mm), Q4AE70 (Rn)
BRENDA 2.1.1.125
ChEMBL Target CHEMBL5406 (Hs), CHEMBL5538 (Mm)
Ensembl Gene ENSG00000142453 (Hs), ENSMUSG00000032185 (Mm), ENSRNOG00000031129 (Rn)
Entrez Gene 10498 (Hs), 59035 (Mm), 363026 (Rn)
Human Protein Atlas ENSG00000142453 (Hs)
KEGG Enzyme 2.1.1.125
KEGG Gene hsa:10498 (Hs), mmu:59035 (Mm), rno:363026 (Rn)
OMIM 603934 (Hs)
Pharos Q86X55 (Hs)
UniProtKB Q86X55 (Hs), Q9WVG6 (Mm), Q4AE70 (Rn)
Wikipedia CARM1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Coactivator-associated arginine methyltransferase 1 (PRMT4) crystalised with inhibitor TP-064.
PDB Id:  5U4X
Ligand:  TP-064
Resolution:  1.88Å
Species:  Human
References: 
Image of receptor 3D structure from RCSB PDB
Description:  CARM1 bound with compound 43.
PDB Id:  7FAJ
Ligand:  compound 43 [PMID: 34781683]
Resolution:  2.25Å
Species:  Human
References:  8
Enzyme Reaction Click here for help
EC Number: 2.1.1.125

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MS049 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.0 pKd 6
⤷ pKd 7.0 (Kd 1x10-7 M) [6]
Description: Isothermal titration calorimetry (ITC) in the presence of SAH
MS023 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pKi 1
⤷ pKi 7.6 (Ki 2.3x10-8 M) [1]
iCARM1 Small molecule or natural product Hs Inhibition 6.2 pKi 4
⤷ pKi 6.2 (Ki 6.785x10-7 M) [4]
Description: Binding affinity determiend by SPR assay.
BIIB021 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >8.0 pIC50 5
⤷ pIC50 >8.0 (IC50 <1x10-8 M) [5]
Description: In vitro methylation of H3 (1-25).
MS049 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pIC50 6
⤷ pIC50 7.5 (IC50 3.4x10-8 M) [6]
BMS pyrazole inhibitor 7f Small molecule or natural product Hs Inhibition 7.4 pIC50 3
⤷ pIC50 7.4 (IC50 4x10-8 M) [3]
SGC2085 Small molecule or natural product Primary target of this compound Hs Inhibition 7.3 pIC50 2
⤷ pIC50 7.3 (IC50 5x10-8 M) [2]
compound 17f [PMID: 19632837] Small molecule or natural product Hs Inhibition 7.2 pIC50 7
⤷ pIC50 7.2 (IC50 7x10-8 M) [7]
compound 43 [PMID: 34781683] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.4 pIC50 8
⤷ pIC50 5.4 (IC50 3.7x10-6 M) [8]
Description: Inhibitor potency vs. enzyme activity.
iCARM1 Small molecule or natural product Hs Inhibition 4.9 pIC50 4
⤷ pIC50 4.9 (IC50 1.23x10-5 M) [4]
Description: Inhibition of CARM1-mediated substrate peptide methylation in vitro.
Inhibitor Comments
BMS pyrazole inhibitor 7f appears to be selective for PRMT4 (CARM1) across a panel of tested proteins [3].

References

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1. Eram MS, Shen Y, Szewczyk MM, Wu H, Senisterra G, Li F, Butler KV, Kaniskan U, Speed BA, dela Sena C et al.. (2015) A Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases. ACS Chemical Biology, Just Accepted Manuscript.

2. Ferreira de Freitas R, Eram MS, Smil D, Szewczyk MM, Kennedy S, Brown PJ, Santhakumar V, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M et al.. (2016) Discovery of a Potent and Selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening. J Med Chem, 59 (14): 6838-47. [PMID:27390919]

3. Huynh T, Chen Z, Pang S, Geng J, Bandiera T, Bindi S, Vianello P, Roletto F, Thieffine S, Galvani A et al.. (2009) Optimization of pyrazole inhibitors of Coactivator Associated Arginine Methyltransferase 1 (CARM1). Bioorg Med Chem Lett, 19 (11): 2924-7. [PMID:19419866]

4. Peng BL, Ran T, Chen X, Ding JC, Wang ZR, Li WJ, Liu W. (2024) A CARM1 Inhibitor Potently Suppresses Breast Cancer Both In Vitro and In Vivo. J Med Chem, 67 (10): 7921-7934. [PMID:38713486]

5. SGC. TP-064 A Chemical Probe For PRMT4. Accessed on 05/04/2017. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/TP-064

6. Shen Y, Szewczyk MM, Eram MS, Smil D, Kaniskan HÜ, Ferreira de Freitas R, Senisterra G, Li F, Schapira M, Brown PJ et al.. (2016) Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. J Med Chem, 59 (19): 9124-9139. [PMID:27584694]

7. Wan H, Huynh T, Pang S, Geng J, Vaccaro W, Poss MA, Trainor GL, Lorenzi MV, Gottardis M, Jayaraman L et al.. (2009) Benzo[d]imidazole inhibitors of Coactivator Associated Arginine Methyltransferase 1 (CARM1)--Hit to Lead studies. Bioorg Med Chem Lett, 19 (17): 5063-6. [PMID:19632837]

8. Zhang Z, Guo Z, Xu X, Cao D, Yang H, Li Y, Shi Q, Du Z, Guo X, Wang X et al.. (2021) Structure-Based Discovery of Potent CARM1 Inhibitors for Solid Tumor and Cancer Immunology Therapy. J Med Chem, 64 (22): 16650-16674. [PMID:34781683]

How to cite this page

2.1.1.- Protein arginine N-methyltransferases: coactivator associated arginine methyltransferase 1. Last modified on 09/05/2024. Accessed on 02/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1255.