SM311

SM311 : Covalent Inhibitor of LIMK1

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

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Probe SM311 is in the process of SERP review.

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Information

LIMK1

Covalent Inhibitor

100 nM up to 1 uM

Additional Data

SGC image SGC Chemical Probe Collection

In Vitro Validations

Uniprot ID: P53667

Target Class: Kinase

Target SubClass: TKL

Potency: Ki

Potency Value: 40.71 nM

Potency Assay: TR-FRET assay (Kinact = 0.00283 s-1, Kinact/ KI = 69516 M-1s-1)

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.5c01204

Uniprot ID: P53667

Target Class: Kinase

Target SubClass: TKL

Potency: Kd

Potency Value: 608 nM

Potency Assay: SPR noncovalent interaction with LIMK1/C349A

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.5c01204

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): LIMK2: NanoBRET (EC50 = 6.74 µM)

Potency assay (off target): DSF panel: 3 targets > 3 K: LIMK1 (deltaTm = 8.11 K), MAPK8 (deltaTm =7.36 K) , MAPK10 (deltaTm =8.12 K).

Potency assay, off target (cells): Selectivity for LIMK1 was confirmed by whole-cell proteomics in HEK293 cells

Potency assay, off target (cells): NanoBRET analysis against a panel of 192 kinases at 1 μM compound concentration. Most significant target engagement, was found to be LIMK1 (91%), followed by CDKL2 (85%), NLK (73%), TXK (73%), AAK1 (66%), and JNK2 (65%). In dose–response assays showed that all targets were only weakly inhibited, with the most potently inhibited off-target (CDKL2) showing only an EC50 of 1.51 μM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

SM311 is a covalent, Type I inhibitor of LIMK1 that leverages a unique Cys residue in the LIMK1 P-loop to achieve remarkable selectivity against the closely related LIMK2. SM311 is the first isoform-selective inhibitor of LIMK1. SM311 is potent against LIMK1 (NanoBRET IC50 = 45 nM), and the only off-target of note is CDKL2 (still >30-fold selectivity window in cells). SM311 should be used alongside the matched negative control (16 in Mandel et al. 2025), as well as a potent dual LIMK1/2 inhibitor (TH470 or LIMK-i3), to conclusively assign cellular phenotypes to LIMK1 activity. SM311 has not been profiled for in vivo exposure/PK as of August 2025 and is therefore suitable for only in vitro experiments without further characterization.

(last updated: 11 Aug 2025 )