LIMK1 Inhibitor

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

GLPG3312 (Compound 28) is an orally active SIK inhibitor with IC₅₀ values of 2.0 nM, 0.7 nM and 0.6 nM for SIK1, SIK2 and SIK3, respectively. GLPG3312 exhibits anti-inflammatory and immunomodulatory activity in vitro on human primary myeloid cells and in vivo in mouse models. GLPG3312 has good oral bioavailability and can be used for research on inflammatory and immune diseases.

SM1-71 (compound 5) is a potent TAK1 inhibitor, with a K_i of 160 nM, it also can covalently inhibit MKNK2, MAP2K1/2/3/4/6/7, GAK, AAK1, BMP2K, MAP3K7, MAPKAPK5, GSK3A/B, MAPK1/3, SRC, YES1, FGFR1, ZAK (MLTK), MAP3K1, LIMK1 and RSK2. SM1-71 can inhibit proliferation of multiple cancer cell lines.

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.

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.

LIMK1-IN-3 is a LIMK1 inhibitor with an IC₅₀ of 4.4 μM. LIMK1-IN-3 shows potential for use in cancer-related research.

S3 peptide is a multifunctional synthetic peptide that acts as a LIMK1 inhibitor with an IC₅₀ of 40 μg/mL. S3 peptide blocks cofilin phosphorylation and SDF-1α (HY-P4911)-induced T cell chemotaxis, and reduces viral particle production of HIV-1 and M-PMV. S3 peptide forms dimers via intermolecular disulfide bonds to bind and disrupt LPS micelles, exerting anti-Gram-negative bacterial activity. S3 peptide serves as a targeting moiety for NKA α1 and is used for the construction of PET tracers. S3 peptide is applicable to research related to HIV-1 infection, M-PMV infection, breast cancer, liver cancer and non-small cell lung cancer.

R-10015, a broad-spectrum antiviral compound for HIV infection, acts as a potent and selective inhibitor of LIM domain kinase (LIMK) and binds to the ATP-binding pocket, with an IC₅₀ of 38 nM for human LIMK1.

SR7826 is a class of bis-aryl urea derived potent, selective and orally active LIM kinase (LIMK) inhibitor with an IC₅₀ of 43 nM for LIMK1. SR7826 is >100-fold more selective for LIMK1 than ROCK and JNK kinases.

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.

8β,9α-Dihydroxylindan-4(5),7(11)-dien-8alpha,12-olide (compound 3), a sesquiterpene, has anti-LIMK1 activity. 8β,9α-Dihydroxylindan-4(5),7(11)-dien-8alpha,12-olide has inhibitory property on cell motility.

LIMK1 inhibitor 1 (compound 24) is a LIMK1 inhibitor. LIMK1 inhibitor 1 can be used in anti-cancer research.

CZh226 is a selective PAK4 inhibitor with an IC₅₀ of 0.0111 μM and a K_i of 0.009 μM. CZh226 functionally inhibits PAK4 activity and reduces the phosphorylation level of downstream signaling molecules. CZh226 inhibits the migration and invasion of tumor cells. CZh226 is applicable to lung cancer-related 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.