GSK591

GSK591 : protein substrate competitive, SAM uncompetitive inhibitor of PRMT5

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(1 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

PRMT5

protein substrate competitive inhibitor, SAM uncompetitive inhibitor

10 nM - 1 uM

DOI - 10.1021/acsmedchemlett.5b00380

Probe Availability:

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:

Unknown

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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 )