MR24

MR24 : Inhibitor of STK24, STK26

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

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Information

STK24
STK26

Inhibitor

up to 1 uM

In Vitro Validations

Uniprot ID: Q9Y6E0

Target Class: Kinase

Target SubClass: STE

Potency: ΔTm

Potency Value: 10.6 ± 0.1 °C

Potency Assay: DSF

PDB ID for probe-target interaction (3D structure): 8QLR

Target aliases:

Serine/threonine-protein kinase 24, STK3, MST3, ST ...

DOI Reference: 10.1021/acs.jmedchem.3c02217

Uniprot ID: Q9Y6E0

Target Class: Kinase

Target SubClass: STE

Potency: EC50

Potency Value: 81 nM

Potency Assay: NanoBRET lysed mode

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

Target aliases:

Serine/threonine-protein kinase 24, STK3, MST3, ST ...

DOI Reference: 10.1021/acs.jmedchem.3c02217

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Selective in a panel of 100 kinases: in the DSF panel assay against 100 kinases, MR24 (24) stabilized only 8 kinases (MST3, MST4, PAK1, NEK2, STLK3, CK1e, FES, and MAP3K5) by more than 50% compared with a corresponding reference compound.

Potency assay, off target (cells): MR24 showed no cellular binding for MST1/2 in NanoBRET assays (EC50 values >50 μM). MR24 only weakly bound to NEK2, CK1e, and FES, with EC50 values in the micromolar range. Other potential off-targets, PAK1, STK39, and MAP3K5, remain to be addressed in future studies, as currently no NanoBRET assays are available for these targets.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

MR24 is an inhibitor of MST3 and MST4. The approach to measuring selectivity was by screening a representative panel of kinases using DSF (thermal shift) in vitro and then testing kinases with an observed thermal shift using NanoBRET target engagement in cells to understand the potential cellular liabilities. I think this approach is limited by the fact that thermal shift measurements are difficult to connect quantitatively with target occupancy and also prone to false negatives. Thus, in my opinion, there is not an adequate selectivity data set to support the use of MR24 as a chemical probe for MST3 and MST4 at this time, although the current data set is encouraging. An additional data set determining selectivity broadly via either an in vitro binding/activity assay and/or using live cell selectivity profiling via NanoBRET would help to fill in the gaps.

(last updated: 4 Apr 2024 )

SERP Ratings

In Cell Rating

SERP Comments:

STK24 pharmacology may dominate at concentrations in the 10 nM - 100 nM range.

(last updated: 25 Apr 2024 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

Cell potency was at the maximum limit of 1 micromolar.

(last updated: 23 May 2024 )