LIMK2 Inhibitor

BMS-5 (LIMKi 3) is a potent LIMK inhibitor with IC₅₀s of 7 nM and 8 nM for LIMK1 and LIMK2, respectively.

BMS-3 is a potent LIMK inhibitor with IC₅₀s of 5 nM and 6 nM for LIMK1 and LIMK2, respectively.

TH-257 is a potent inhibitor of LIMK1 and LIMK2 with IC₅₀ values of 84 nM and 39 nM for LIMK1 and LIMK2, respectively, and it can be used as a chemical probe for LIMK1 and LIMK2. TH-257 is an allosteric inhibitor targeting a binding pocket induced by an αC and DFG-out conformation. TH257 is exquisitely selective and no significant activity against the wider kinome has been observed in the KINOMEscan assay at 1 μM.

T56-LIMKi is a selective inhibitor of LIMK2; inhibits the growth of Panc-1 cells with an IC₅₀ of 35.2 μM.

TH251 is a LIMK1 and LIMK2 inhibitor with IC₅₀s of 52 nM and 47 nM against LIMK1 and LIMK2, respectively. TH251 binds to inactive αC-out and DFG-out LIMK1 conformations, inhibits unphosphorylated LIMK1 and LIMK2 enzymatic activity, and exhibits unchanged potency despite PAK-mediated phosphorylation of either kinase. TH251 can be used for the research of cancers, glaucoma, and CNS diseases.

TH470 is a highly selective LIMK1/2 (LIM kinase1/2) inhibitor (LIMK1 IC₅₀=9.8 nM; LIMK2 IC₅₀=13 nM), and can be used in orphan disease research.

CRT0105950 is a potent LIMK inhibitor, with IC₅₀s of 0.3 nM and 1 nM for LIMK1 and LIMK2 respectively. CRT0105950 can be used for the research of cancer.

LIMK1 inhibitor BMS-4 is a LIM Kinase (LIMK) inhibitor targeting to LIMK1/2. LIMK1 inhibitor BMS-4 inhibits phosphorylation of cofilin, the LIMK substrate. However, LIMK1 inhibitor BMS-4 is noncytotoxic on A549 cells.

LIMK-IN-1 (Compound 14) is an inhibitor of LIM-Kinase (LIMK), with IC₅₀s of 0.5 nM and 0.9 nM for LIMK1 and LIMK2, respectively. LIMK-IN-1 can be used for ocular hypertension and associated glaucoma research.

MDI-117740 is a dual LIMK1/2 inhibitor. MDI-117740 shows effective cellular target engagement with LIMK1 (pIC₅₀ = 6.73) and LIMK2 (pIC₅₀ = 7.18) in HEK293 cells. MDI-117740 exerts significant anti-migratory activity in MDA-MB-231 cells. MDI-117740 can be used for the study of cancers and neurodegenerative disorders.

SM311 (Compound 10), a chemical probe, is a potent selective irreversible LIMK1 inhibitor (EC₅₀=0.045 μM, >30-fold selective over LIMK2). SM311 blocks cofilin phosphorylation and actin cytoskeleton regulation. SM311 is promising for research of neurodegenerative diseases like Fragile X syndrome (FXS) and Alzheimer’s disease, as well as tumor invasion.

LIMK-IN-3 (Compound 33) is a LIMK2 inhibitor (IC₅₀: 1.2 nM). LIMK-IN-3 can be used for glaucoma research.

LX7101 monohydrochloride is a potent LIM-kinase, ROCK and PKA inhibitor with IC₅₀s of 24 nM, 1.6 nM, 10 nM and <1 nM for LIMK1, LIMK2, ROCK2 and PKA, respectively. LX7101 monohydrochloride proves significantly selective for LIMK2 with IC₅₀ values of 4.3 nM and 32 nM for LIMK2 and LIMK1 at 2 μM ATP, respectively. LX7101 monohydrochloride has the potential for ocular hypertension and associated glaucoma research.