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protein arginine methyltransferase 5

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Target not currently curated in GtoImmuPdb

Target id: 1256

Nomenclature: protein arginine methyltransferase 5

Abbreviated Name: PRMT5

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 - 637 14q11.2 PRMT5 protein arginine methyltransferase 5
Mouse - 637 14 C2 Prmt5 protein arginine N-methyltransferase 5
Rat - - 15p13 Prmt5 protein arginine methyltransferase 5
Previous and Unofficial Names Click here for help
Histone-arginine N-methyltransferase | Jak-binding protein 1 | Jbp1 | HRMT1L5
Database Links Click here for help
Alphafold O14744 (Hs), Q8CIG8 (Mm)
ChEMBL Target CHEMBL1795116 (Hs)
Ensembl Gene ENSG00000100462 (Hs), ENSMUSG00000023110 (Mm), ENSRNOG00000012046 (Rn)
Entrez Gene 10419 (Hs), 27374 (Mm), 364382 (Rn)
Human Protein Atlas ENSG00000100462 (Hs)
KEGG Gene hsa:10419 (Hs), mmu:27374 (Mm), rno:364382 (Rn)
OMIM 604045 (Hs)
Pharos O14744 (Hs)
SynPHARM 81924 (in complex with EPZ015666)
83227 (in complex with GSK591)
UniProtKB O14744 (Hs), Q8CIG8 (Mm)
Wikipedia PRMT5 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  PRMT5/MEP50 crystal structure with MTA and MRTX-1719 bound
PDB Id:  7S1S
Ligand:  MRTX1719
Resolution:  2.62Å
Species:  Human
References:  8
Image of receptor 3D structure from RCSB PDB
Description:  PRMT5:MEP50 complexed with inhibitor PF-06939999
PDB Id:  7MX7
Ligand:  PF-06939999
Resolution:  2.49Å
Species:  Human
References:  4
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of PRMT5:MEP50 in complex with MTA and TNG908
PDB Id:  8VEY
Ligand:  TNG908
Resolution:  0.0Å
Species:  Human
References:  3

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MRTX1719 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.9 pKd 8
⤷ pKd 9.9 (Kd 1.4x10-10 M) [8]
Description: Binding affinity to PPRMT5 complexed with MTA
onametostat Small molecule or natural product Ligand has a PDB structure Hs Inhibition >9.2 pKd 2
⤷ pKd >9.2 (Kd <6.28x10-10 M) [2]
Description: Equilibrium dissociation constant determined by surface plasmon resonance spectroscopy, using immobilized Avi-tagged PRMT5:MEP50 protein on streptavidin coated sensors.
TNG908 Small molecule or natural product Ligand has a PDB structure Hs Binding 8.7 – 9.5 pKd 3
⤷ pKd 9.5 (Kd 3x10-10 M) [3]
Description: Affinity for MTA-PRMT5 complex
pKd 8.7 (Kd 1.9x10-9 M) [3]
Description: Affinity for apoPRMT5
EPZ015666 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.3 pKi
⤷ pKi 8.3 (Ki 5x10-9 M)
TNG908 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.1 pIC50 3
⤷ pIC50 8.1 (IC50 9x10-9 M) [3]
Description: Inhibition of PRMT5 determined by an SDMA in-cell western assay in the HAP1 MTAP-isogenic cell line
GSK591 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.0 pIC50 5
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [5]
Description: Measuring inhibition of methylation of histone H4 in an in vitro biochemical assay.
MRTX1719 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.9 pIC50 8
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [8]
Description: Inhibitory potency in HCT116 MTAP-deleted cells
LLY-283 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.7 pIC50 6
⤷ pIC50 7.7 (IC50 2x10-8 M) [6]
Description: Inhibition of methylation of an H4R3 derived peptide substrate in vitro.
DS-437 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.2 pIC50 7
⤷ pIC50 5.2 (IC50 5.9x10-6 M) [7]
cmp5 [PMID: 25742700] Small molecule or natural product Primary target of this compound Hs Inhibition - - 1
⤷ [1]
PF-06939999 Small molecule or natural product Ligand has a PDB structure Hs Inhibition - - 4
⤷ [4]

References

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1. Alinari L, Mahasenan KV, Yan F, Karkhanis V, Chung JH, Smith EM, Quinion C, Smith PL, Kim L, Patton JT et al.. (2015) Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation. Blood, 125 (16): 2530-43. [PMID:25742700]

2. Brehmer D, Beke L, Wu T, Millar HJ, Moy C, Sun W, Mannens G, Pande V, Boeckx A, van Heerde E et al.. (2021) Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity. Mol Cancer Ther, 20 (12): 2317-2328. [PMID:34583982]

3. Cottrell KM, Briggs KJ, Whittington DA, Jahic H, Ali JA, Davis CB, Gong S, Gotur D, Gu L, McCarren P et al.. (2024) Discovery of TNG908: A Selective, Brain Penetrant, MTA-Cooperative PRMT5 Inhibitor That Is Synthetically Lethal with MTAP-Deleted Cancers. J Med Chem, [Epub ahead of print]. [PMID:38595098]

4. Jensen-Pergakes K, Tatlock J, Maegley KA, McAlpine IJ, McTigue M, Xie T, Dillon CP, Wang Y, Yamazaki S, Spiegel N et al.. (2022) SAM-Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance. Mol Cancer Ther, 21 (1): 3-15. [PMID:34737197]

5. SGC. GSK591 A chemical probe for PRMT5. Accessed on 11/12/2015. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/GSK591

6. SGC. LLY-283 A Chemical Probe For PRMT5. Accessed on 05/04/2017. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/LLY-283283

7. Smil D, Eram MS, Li F, Kennedy S, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M, Schapira M. (2015) Discovery of a Dual PRMT5-PRMT7 Inhibitor. ACS Med Chem Lett, 6 (4): 408-12. [PMID:25893041]

8. Smith CR, Aranda R, Bobinski TP, Briere DM, Burns AC, Christensen JG, Clarine J, Engstrom LD, Gunn RJ, Ivetac A et al.. (2022) Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers. J Med Chem, 65 (3): 1749-1766. [PMID:35041419]

How to cite this page

2.1.1.- Protein arginine N-methyltransferases: protein arginine methyltransferase 5 . Last modified on 10/04/2024. Accessed on 07/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1256.