MDI-114215

MDI-114215 : Inhibitor of LIMK1, LIMK2

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

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Probe MDI-114215 is in the process of SERP review.

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Information

LIMK1
LIMK2

Inhibitor

up to 300 nM

In Vitro Validations

Uniprot ID: P53667

Target Class: Kinase

Target SubClass: TKL

Potency: Kd

Potency Value: 33 nM

Potency Assay: Eurofins DiscoverX KdELECT

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.4c02694

Uniprot ID: P53667

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 13 nM

Potency Assay: Enzymatic inhibition of PAK1-phosphorylated LIMK1/2 (PAK1-pLIMK1/2)

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.4c02694

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Wider kinome profiling was performed on MDI-114215 using the Eurofins/DiscoverX scanMAX panel of 468 kinases at 300 nM, providing S35 of 0.01 for LIMK1/2.

Potency assay (off target): Off-target pharmacological activity in a panel of receptors, ion channels, transporters and enzymes using the CEREP SafetyScreen44 panel in addition to key safety liabilities was assessed. There were no major liabilities against hERG (IC50 > 10 μM) and minimal off-target activities were identified. CYP450 profiling showed moderate inhibition of CYP3A4 and CYP2C9 (IC50 = 3.6 μM and 5.5 μM, respectively).

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Despite several reported tool compounds for LIMK1/2 many of which suffer from low overall kinase selectivity. The dual LIMK1/2 inhibitor MDI-114215 is a well-characterized chemical probe. It shows good kinase selectivity against 468 kinases when tested at 300nM compound concentration (please note: this is only 10fold above the IC50 values for LIMK1/2). Therefore it is important not to overdose the compound in cellular assays and carefully assess in vivo results (peak/trough ratio!).

(last updated: 25 Feb 2025 )