TP-064

TP-064 : Inhibitor of CARM1

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe TP-064 is in the process of SERP review.

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Information

CARM1

Inhibitor

up to 1 uM

Additional Data

SGC Chemical Probe Collection

Probe Availability:

In Vitro Validations

Uniprot ID: Q86X55

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: Kd

Potency Value: 7.1 ± 1.8 nM

Potency Assay: SPR

PDB ID for probe-target interaction (3D structure): 5U4X

Target aliases:

Histone-arginine methyltransferase CARM1, PRMT4, C ...

DOI Reference: 10.18632/oncotarget.24883

Uniprot ID: Q86X55

Target Class: Epigenetic

Target SubClass: Methyltransferase

Potency: ΔTm

Potency Value: + 6 °C

Potency Assay: Differential static light scattering (DSLS), aggregation temperature

PDB ID for probe-target interaction (3D structure): 5U4X

Target aliases:

Histone-arginine methyltransferase CARM1, PRMT4, C ...

DOI Reference: 10.18632/oncotarget.24883

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

TP-064 showed high selectivity for PRMT4 over other PRMTs (> 100 fold). It was inactive against the other family members (IC50 > 10 μM) except for PRMT6 (IC50 of 1.3 ± 0.4 μM), which is the most structurally related to PRMT4 among PRMT family and PRMT8 (IC50 of 8.1 ± 0.6 μM). To further assess the selectivity of TP-064, was tested against 24 protein lysine methyltransferases and DNA methyltransferases. TP-064 did not inhibit any of these methyltransferases up to 10 μM. Negative control compound TP-064N was completely inactive against other methyltransferases.

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

(last updated: 22 Mar 2023 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

Highly potent probe with very good selectivity against other PRMTs and 24 other protein lysine methyltransferases. Structurally very similar negative control compound also tested regarding the selectivity in the PRMT family. Tested in 89 different cancer cell lines, inhibits growth of MM cell lines. Cell viability sufficient, overall the best probe for PRMT4 (which inhibition methylation of target proteins) to date. Another probe for PRMT4 (does not inhibit dimethylation of BAF155): doi.org/10.1002/cmdc.202100018

(last updated: 17 Jun 2024 )

Portal Comments

In a 2023 study, Hu et al. evaluated TP-064 in live-cell assays for Phospholipidosis induction, cautioning about adverse effects at concentrations near 1 uM. (DOI:10.1016/j.chembiol.2023.09.003)

(last updated: 7 Nov 2023)