GSK591 : protein substrate competitive, SAM uncompetitive inhibitor of PRMT5



  • PRMT5
  • protein substrate competitive inhibitor, SAM uncompetitive inhibitor
  • 10 nM - 1 uM

In Vitro Validations

Uniprot ID: O14744
Target Class: Epigenetic
Target SubClass: Protein methyltransferase
Potency: IC50
Potency Value: 4 nM
Potency Assay: Homogeneous time-resolved fluorescence (HTRF) assay under balanced conditions to monitor the monomethylation of H4R3 on a histone H4 peptide by PRMT5:MEP50.
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: Yes. Early SAR exploration around the THIQ motif confirmed the contribution of the cation−π interaction with cofactor SAM and was thus retained within the series as a key binding interaction.
Target aliases:
Protein arginine N-methyltransferase 5, SKB1, JBP1 ...

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): No inhibition of 20 Protein methyltransferases at 50 uM (PRMT8, PRMT1, PRMT3, PRMT6, PRMT7, CARM1, DOT1L, SMYD2, SMYD3, SETD7, EZH1, EZH2, SUV39H1, EHMT1, EHMT2, SETDB1, SETD2, NSD1, WHSC1L1, WHSC1)
Probe Selectivity in Vitro:


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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 18 May 2016 )

SERP Ratings

In Cell Rating

(last updated: 30 May 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

GSK591 is an excellent probe to investigate PRMT5 function in cells. For in vivo work, EPZ015666 is a more suitable compound.

(last updated: 4 Jun 2016 )