TH257

TH257 : Allosteric inhibitor of LIMK1 and LIMK2

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 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

LIMK1
LIMK2

Allosteric, Type III
Allosteric,Type III

up to 1 uM

Additional Data

SGC Chemical Probe Collection

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: P53667

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 84 nM

Potency Assay: RapidFire MS assay

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

Target aliases:

LIM domain kinase 1, LIMK, LIMK1, LIMK1_HUMAN, LIM ...

DOI Reference: 10.1021/acs.jmedchem.2c01106

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): TH257 is exquisitely selective and no significant activity against the wider kinome has been observed in the KINOMEscan assay (Dx) at 1 μM (IC50 >> 50 % inhibition)

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

(last updated: 25 May 2017 )

SERP Ratings

In Cell Rating

SERP Comments:

Selective allosteric molecule for use in cells to probe the effects of LIMK inhibition.

(last updated: 2 Jun 2017 )

SERP Ratings

In Cell Rating

SERP Comments:

Potent and selective chemical probe for LIMK1/2 kinases. TH-257 appears to bear a minor chemical modification from a previously disclosed 40 nM allosteric inhibitor (butyl replacement for a methyl group). Surpasses many of the SGC set criteria for potency and selectivity, and a very weak binding control compound is included. Would be helpful to provide more off-target profiling e.g. against ion channel, GPCRs etc. as well as cell-based activity data (LIMK substrate(s) are known) and ideally showing on-target effect.

(last updated: 20 Jun 2017 )