SM311

SM311 : Covalent Inhibitor of LIMK1

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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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 )

SERP Ratings

In Cell Rating

SERP Comments:

This covalent probe for LMK1 is a useful tool for studying LMK1 biology, when used at the recommended doses between 0.1 and 1uM. SM311 does bind additional targets at higher concentrations, including CDKL2 and LIMK2, which could confound conclusions. It is highly recommended to use the negative control compound SM311-NC for comparisons with SM311 and interpretation of results.

(last updated: 19 Aug 2025 )