GSK-3 Inhibitor

TC-G 24 (Compound 24) is a potent, selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC₅₀ of 17.1 nM. TC-G 24 can cross the BBB and can be used for studying many diseases such as type 2 diabetes mellitus, stroke, Alzheimer, and other related diseases.

3-Methylthienyl-carbonyl-JNJ-7706621 is a potent and selective inhibitor of cyclin-dependent kinase (CDK), with IC₅₀s of 6.4 nM and 2 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. 3-Methylthienyl-carbonyl-JNJ-7706621 also shows potent inhibition of GSK-3 (IC₅₀=0.041 μM) and modest potency against CDK4, VEGF-R2, and FGF-R2 (IC₅₀=0.11, 0.13, 0.22 μM, respectively). 3-Methylthienyl-carbonyl-JNJ-7706621 can be used for the research of cancer.

Protein kinase inhibitor 11 (Compound I-96) is a protein kinase inhibitor that can inhibit the activity of PIM-1, CDK-2, GSK-3, and SRC. Protein kinase inhibitor 11 holds promise for research in cancer, immune disorders, and neurodegenerative diseases.

GSK-3β inhibitor 15 (Compound 54) is a GSK-3β inhibitor (IC₅₀: 3.4 nM). GSK-3β inhibitor 15 inhibits Aβ_1-42-induced GSK-3β and tau protein phosphorylation. GSK-3β inhibitor 15 inhibits LPS-induced iNOS expression. GSK-3β inhibitor 15 has neuroprotective effects on Aβ_1-42-induced neurotoxicity. GSK-3β inhibitor 15 can be used for research of Alzheimer’s disease (AD).

GSK-3β inhibitor 17 (compound 5 n) is a potent GSK-3β inhibitor. GSK-3β inhibitor 17 decreases cisplatin (HY-17394) induced p-p65, KIM-1 protein and mRNA expression. GSK-3β inhibitor 17 decreases cisplatin induced TNF-α, IL-1β, IL-6 and MCP-1 mRNA expression. GSK-3β inhibitor 17 shows anti-inflammation effect and has the potential for the research of acute kidney injury.

FRATtide is a peptide derived from the GSK-3 binding protein that inhibits the phosphorylation of Axin and β-catenin. FRATtide inhibits GSK-3 binding to Axin.

BChE-IN-49 is an orally active BChE inhibitor with IC₅₀ values of 0.73 μM and 6.43 μM against BChE and AChE, respectively. BChE-IN-49 reduces AChE levels to inhibit the degradation of acetylcholine. By inhibiting GSK-3β, BChE-IN-49 potently activates the Wnt/β-catenin signaling pathway, exerting potent anti-Aβ, antioxidant, anti-neuroinflammatory and anti-apoptotic effects. BChE-IN-49 can be used in research related to Alzheimer's disease.

JNK3/Wnt/β-catenin modulator-1 is a brain-penetrant JNK3 inhibitor and Wnt/β-catenin activator. JNK3/Wnt/β-catenin modulator-1 decreases Aβ_1-42 production and reduced ROS generation. JNK3/Wnt/β-catenin modulator-1 inhibits the activation of JNK and Puma, promotes Beclin-1 expression, reduces GSK-3β and BACE1 expression and activates Wnt/β-catenin signaling. JNK3/Wnt/β-catenin modulator-1 improves cognitive and memory performance, attenuates histopathological brain damage, preserves structure of hippocampal pyramidal cells and cerebral cortical neurons. JNK3/Wnt/β-catenin modulator-1 can be used for the research of Alzheimer's disease.

hAChE-IN-5 (compound 49) is a potent hAChE and hBuChE inhibitor with IC₅₀ values of 0.17 μM and 0.17 μM, respectively. hAChE-IN-5 shows potent GSK3β inhibition with an IC₅₀ value of 0.21 μM. hAChE-IN-5 is used as tau protein aggregation and Aβ1-42 self-aggregation inhibitor. hAChE-IN-5 can bind virtually with the PAS affecting Aβ aggregation, thus preventing Aβ-dependent neurotoxicity. hAChE-IN-5 can penetrate BBB and has the potential for multi-targeted anti-Alzheimer's agents research.

JNK3 inhibitor-5 (Compound 22b) is a potent and selective JNK3 inhibitor with an IC₅₀ of 0.379 nM. JNK3 inhibitor-5 effectively protects the neuronal cells against amyloid beta-induced apoptosis. JNK3 inhibitor-5 has a high cell permeability and is predicted as BBB permeable.

GSK-3β inhibitor 27 (Compound 1c) is a reversible and competitive GSK-3β inhibitor with an IC₅₀ value of 2.2 μM. GSK-3β inhibitor 27 inhibits tau hyperphosphorylation, reduces Aβ protein aggregation and possesses metal chelation and neuroprotective potential. GSK-3β inhibitor 27 is promising for research of neurodegenerative diseases (such as Alzheimer’s disease).

Fyn-IN-1 (Compound 43) is a selective, blood-brain barrier permeable Fyn and GSK-3β inhibitor with IC₅₀ values of 0.044 μM and 0.61 μM, respectively. Fyn-IN-1 significantly downregulates the pro-inflammatory enzyme iNOS. Fyn-IN-1 can be used in the research of neurodegenerative diseases.

GSK-3β/G9a-IN-1 (Compound T2) is an orally active, selective, blood-brain-barrier permeable, competitive G9a (substrate-competitive, IC₅₀: 1.1 μM) and GSK-3β (ATP competitive, IC₅₀: 0.8 μM) inhibitor. GSK-3β/G9a-IN-1 is a potent H3K9me2 inhibitor that reshapes chromatin landscape. GSK-3β/G9a-IN-1 lowers tau phosphorylation, reduces Aβ aggregation. GSK-3β/G9a-IN-1 displays inhibition toward glucocorticoid receptor, androgen receptor, and alpha-2A adrenergic receptor. GSK-3β/G9a-IN-1 also upregulates SAGA complex members such as Eny2 and Sgf29. GSK-3β/G9a-IN-1 markedly improves memory, restores social behaviors, and increases synaptic complexity in late-onset Alzheimer’s disease.

GSK-3β inhibitor 20 (compound 3A) is an potent inhibitor of GSK-3β with an IC₅₀ value of 74.4 nM.

SCR1693 is a selective, reversible, orally active and noncompetitive inhibitor of AChE (IC₅₀ = 0.68 μM) as well as a calcium channel blocker. SCR1693 reduces tau phosphorylation levels, and inhibits the generation and release of Aβ. SCR1693 restores insulin signaling and improves cognitive deficits. SCR1693 can be used for the study of Alzheimer's disease, especially which complicated with type 2 diabetes mellitus.

GSK-3α/β-IN-1 is GSK-3α/β inhibitor with IC₅₀ s of 0.265 μM and 0.255 μM for GSK-3α and GSK-3β, respectively. GSK-3α/β-IN-1 also inhibits PKA with an IC₅₀ of 0.188 μM. GSK-3α/β-IN-1 potently inhibits cell viability of three Glioblastoma (GBM) cell lines (IC₅₀ : 3-6 μM, 72 h) with no toxicity to human astrocytes and good metabolic stability. GSK-3α/β-IN-1 has potential CNS activity in all-human blood-brain barrier (BBB) model of GBM.

GSK-3β/HDAC-IN-2 is a potent inhibitor of GSK-3β (IC₅₀ = 0.04 μM), HDAC2 (IC₅₀ = 1.05 μM, Ki = 0.070 μM) and HDAC6 (IC₅₀ = 1.52 μM, Ki = 0.017 μM). GSK-3β/HDAC-IN-2 inhibits HDAC2 and HDAC6 activities and blocks tau hyperphosphorylation. GSK-3β/HDAC-IN-2 exerts neuroprotective effects and shows no significant toxicity. GSK-3β/HDAC-IN-2 can be used in the research of Alzheimer's disease.

Multi-kinase-IN-13 (Compound 10F) is an inhibitor of AChE, BuChE, and GSK-3β, with an IC₅₀ of 3 nM against hAChE, 303 nM against hBuChE, and 7.58 nM against GSK-3β. Multi-kinase-IN-13 exhibits in vitro iron chelating activity. AChE-IN-110 can be used in the research of Alzheimer's disease.

18BIOder is a neuroprotective GSK-3β inhibitor, highly selectively inhibiting HIV-1.

GSK-3β inhibitor 28 is selective and non-competitivea glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC₅₀ of 14.82 nM. GSK-3β inhibitor 28 can upregulate the expression level of phosphorylated GSK-3β and downregulate the expression of p-NF-κB, P65, C-myc and Cyclin D1. GSK-3β inhibitor 28 can induce cells apoptosis, G1 phase arrest and inhibit migration. GSK-3β inhibitor 28 can be used for the research of cancer, such as colorectal cancer.