GSK-3 Inhibitor

ARN25068 is a sub-micromolar inhibitor of the three protein kinases, GSK-3β, FYN and DYRK1A to tackle tau hyperphosphorylation.

Dammarenediol II is a ginsenoside precursor. Dammarenediol II reduces the activity of O-GlcNAc transferase (OGT) and downregulates the global O-GlcNAcylation level. Dammarenediol II inhibits the phosphorylation of Akt, mTOR and GSK3β. Dammarenediol II inhibits human carboxylesterase activity, VEGF-induced ROS production, stress fiber formation and vascular endothelial cadherin disruption. Dammarenediol II promotes cell apoptosis (apoptosis), increases the levels of cleaved PARP1 and p53, and inhibits retinal microvascular leakage. Dammarenediol II can be used in studies related to liver cancer and diabetic retinopathy.

Cu(II)GTSM, a cell-permeable Cu-complex, significantly inhibits GSK3β. Cu(II)GTSM inhibits Amyloid-β oligomers (AβOs) and decreases tau phosphorylation. Cu(II)GTSM also decreases the abundance of Amyloid-β trimers. Cu(II)GTSM is a potential anticancer and antimicrobial agent.

Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC₅₀s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes.

A 1070722 is a potent and selective glycogen synthase kinase 3 (GSK-3) inhibitor, with a K_i of 0.6 nM for both GSK-3α and GSK-3β. A 1070722 can penetrate the blood-brain barrier (BBB) and accumulates in brain regions, thus potential for PET radiotracer for the quantification of GSK-3 in brain. A 1070722 decreases spontaneous locomotion.

BRD3731 is a selective GSK3β inhibitor, with IC₅₀s of 15 nM and 215 nM for GSK3β and GSK3α, respectively. BRD3731 is potentail for the research of post-traumatic stress disorder (PTSD), psychiatric disorder, diabetes, and neurodegenerative disorders.

PPA24 is a PP2A activator with a K_D of 8.465 μM for PP2ACα. PPA24 induces cancer cell death via apoptosis. PP2ACα induces ROS generation and decreases the level of c-Myc expression. PPA24 can be used to study colorectal cancer (CRC), Folinic acid (HY-17556), 5-Fluorouracil (HY-90006), and Oxaliplatin (HY-17371) (FOLFOX)-resistant CRC, and melanoma cancer.

RGB-286638 free base is a potent inhibitor of CDK and MAPK9. RGB-286638 free base inhibits the activities of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3 and p35-CDK5, with IC₅₀ values of 1, 2, 3, 4, 5 and 5 nM, respectively. RGB-286638 free base inhibits GSK-3β and TAK1, with IC₅₀ values of 3 nM and 5 nM, respectively. RGB-286638 free base induces caspase-dependent Apoptosis in cells. RGB-286638 free base delays tumor growth in an orthotopic glioblastoma mouse model. RGB-286638 free base extends survival in multiple myeloma models. RGB-286638 free base can be used in research related to glioblastoma and multiple myeloma.

EHT 5372 is a highly potent and selective inhibitor of DYRK's family kinases with IC₅₀s of 0.22, 0.28, 10.8, 93.2, 22.8, 88.8, 59.0, 7.44, and 221 nM for DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK4, GSK-3α, and GSK-3β, respectively.

Manzamine A hydrochloride, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC₅₀s of 10.2 μM and 1.5 μM, respectively. Manzamine A hydrochloride targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A hydrochloride has antimalarial and anticancer activities. Manzamine A hydrochloride also shows potent activity against HSV-1.

CDKL5/GSK3-IN-1 (Compound 2) is a potent and selectivity chemical probe for CDKL5/GSK3.CDKL5/GSK3-IN-1 has potent inhibition of CDKL5 and GSK3α/β, with IC₅₀ values of 4.6, 24 and 9.5 nM for CDKL5, GSK3β and GSK3α, respectively, in the NanoBRET assay. CDKL5/GSK3-IN-1 can be used for the research of CNS diseases.

Benarthin is an orally active Pyroglutamyl peptidase inhibitor, THY1 inhibitor (with a K_d value of 5.13e-08 M) and competitive PGP-1 inhibitor (K_i = 1.2 µM). Benarthin is isolated from the culture broth of Streptomyces xanthophaeus MJ244-SF1. Benarthin disrupts the THY1-SFRP1 interaction, inhibits the activation of the GSK3α/β-β-catenin pathway, and reduces the upregulation of FASLG. Benarthin attenuates urothelial anoikis and reduces cell Apoptosis. Benarthin possesses iron-chelating activity. Benarthin maintains urothelial barrier integrity and blocks the pathological cascade of renal interstitial fibroblasts induced by HAP stimulation. Benarthin can be used in studies related to kidney stones.

Sodium thiosulfate (Sodium hyposulfite) is an antioxidant. Sodium thiosulfate inhibits the expression of p-GSK-3β and β-catenin proteins, reduces IL-1β, COX-2, and Iba-1, and inhibits NFκB activation. Sodium thiosulfate promotes angiogenesis, inhibits inflammation, and improves acute lung injury. Sodium thiosulfate also exhibits anti-cancer activity against melanoma. Sodium thiosulfate also exerts renal protective effects. Sodium thiosulfate can be used in the research of osteoarthritis, brain inflammation, cancer (such as breast cancer, melanoma), and kidney disease.

GSK-3β inhibitor 22 (compound 20o) is a GSK-3β inhibitor with an IC₅₀ of 3.1 nM. GSK-3β inhibitor 22 has the potential of the study of Alzheimer's disease.

(-)-Syringaresinol is an orally active isomer of syringaresinol (HY-N8307) found in Annona Montana. (-)-Syringaresinol exhibits antioxidant, anti-inflammatory, and anticancer activities. (-)-Syringaresinol can alleviate ulcerative colitis via the PI3K-Akt/MAPK/Wnt signaling pathway. (-)-Syringaresinol inhibits HL-60 cell proliferation by arresting the G1 phase and inducing apoptosis. (-)-Syringaresinol inhibits LPS (HY-D1056)-induced microglial activation by downregulating the NF-κB p65 signaling pathway and its interaction with ERβ, exerting anti-neuroinflammatory effects.

VP3.15 dihydrobromide is a highly potent, orally bioavailable, and CNS-penetrant PDE7-GSK3 dual inhibitor, with IC₅₀ values of 1.59 μM and 0.88 μM against PDE7 and GSK3, respectively. VP3.15 dihydrobromide elevates intracellular cAMP levels, suppresses immune responses, enhances remyelination, limits excessive tau phosphorylation, and alleviates neuroinflammation and neuronal loss. VP3.15 dihydrobromide promotes oligodendrocyte precursor cell differentiation, improves in vivo remyelination, inhibits autoimmune encephalomyelitis, and mitigates germinal matrix-intraventricular hemorrhage-related brain injury, cerebral atrophy, ventricular enlargement, and cognitive impairment. VP3.15 dihydrobromide can be used in research related to multiple sclerosis and germinal matrix-intraventricular hemorrhage.

6'''-Feruloylspinosin is an orally active RORα activator that crosses the blood-brain barrier, with a K_d of 0.308 μM, and is found in natural sources. 6'''-Feruloylspinosin modulates AMPK and mTOR phosphorylation. 6'''-Feruloylspinosin promotes autophagy through the AMPK/mTOR signaling pathway, inhibits GSK3β phosphorylation at Tyr216, and activates the PGC-1α/Nrf2/HO-1 pathway. 6'''-Feruloylspinosin regulates neurotransmitter levels, enhances mRNA expression of GABA_A α1, α5, and GABA_B R1 receptor subunits, increases brain 5-HT and GABA, restores melatonin levels, and ameliorates anxiety-like behaviors. 6'''-Feruloylspinosin regulates oxidative stress homeostasis, inhibits mitochondrial dysfunction, decreases MDA while increasing GSH. 6'''-Feruloylspinosin can be used for research on Alzheimer's disease, acute myocardial infarction, heart failure with insomnia, and insomnia.

CT-1 is a secreted protein belonging to the IL-6 cytokine family. Overexpression of CT-1 enhances cell proliferation, migration and angiogenesis via the ADMA/DDAH pathway. CT-1 inhibits the growth of triple-negative breast cancer cells by simultaneously inducing Ferroptosis in N2-type tumor-associated neutrophils and cancer cells. CT-1 activates the Jak/STAT-3, p42/p44 MAPK and AMPK pathways, and inhibits GSK-3β activity through phosphorylation to induce cardiomyocyte hypertrophy. CT-1 enhances the viability of cardiomyocytes and neurons, reduces cell Apoptosis, induces the expression of heat shock proteins (HSP) and BNP, and inhibits TNF levels. CT-1 exerts anti-tumor activity in mouse models of triple-negative breast cancer. CT-1 improves cognitive impairment in mice. CT-1 is applicable to the research of ischemic heart disease, triple-negative breast cancer, myocardial hypertrophy, Parkinson's disease, hypertensive heart disease, myocardial infarction, acute Chagas cardiomyopathy, high-fat diet-induced cognitive impairment and diabetes-related cognitive impairment.

7BIO (7-Bromoindirubin-3-Oxime) is the derivate of indirubin. 7BIO (7-Bromoindirubin-3-Oxime) has inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β). 7BIO (7-Bromoindirubin-3-Oxime) inhibits Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, activation of astrocytes and microglia, and attenuates Aβ oligomer-induced cognitive impairments in mice^[1].

GSK-3b Inhibitor XI (Compound 33) is a potent and selective GSK3β inhibitor, with a K_i value of 25 nM. GSK-3b Inhibitor XI increases glycogen synthase (GS) activity. GSK-3b Inhibitor XI can be used for research on type 2 diabetes and Alzheimer’s disease.