GSK-3 Inhibitor

GSK-3β inhibitor 24 (Compound 41) is a potent GSK-3β inhibitor with an IC₅₀ of 0.22 nM. GSK-3β inhibitor 24 increases GSK-3β phosphorylation at Ser9 site dose-dependently. GSK-3β inhibitor 24 inhibits the hyperphosphorylation of tau protein by decreasing the p-tau-Ser396 abundance. GSK-3β inhibitor 24 up-regulates β-catenin and neurogenesis-related markers (GAP43 and MAP-2). GSK-3β inhibitor 24 demonstrates remarkable anti-Alzheimer's disease (AD) effects.

GSK-3β-IN-29 is a selective GSK-3β inhibitor with an IC₅₀ of 34.0 nM. GSK-3β-IN-29 shows selectivity for GSK-3β over 40 other kinases and for 5-HT1_a receptor. GSK-3β-IN-29 exhibits neuroprotection in mice. GSK-3β-IN-29 can be used for the research of nervous system (CNS) disorders.

Indirubin-3'-monoxime-5-sulphonic acid is a potent and selective inhibitor of CDK1, CDK5, and GSK-3β with IC₅₀s of 5 nM, 7 nM, and 80 nM, respectively.

GSK-3 inhibitor 6 (2) is a CNS penetrated GSK-3 inhibitor, with IC₅₀ values of 29 nM and 24 nM for GSK-3α and GSK-3β, respectively.

JGK-263 is an orally active Glycogen synthase kinase-3β (GSK-3β) inhibitor. JGK-263 exhibits neuroprotective effect and can improve motor function. JGK-263 can be used for the research of neurological disease, such as amyotrophic lateral sclerosis (ALS).

MAO-B-IN-43 (4) is a potent hMAO-B inhibitor and a weak GSK3β kinase inhibitor, with K_i values of 0.044 μM and 0.004 μM for hMAO-A and hMAO-B, respectively. MAO-B-IN-43 (4) can be used for the research of neurodegenerative disorder.

PIMPC is a compound with antioxidant and metal-chelating properties. PIMPC is a novel inhibitor of glycogen synthase kinase 3 (GSK-3). PIMPC has potential anti-Alzheimer's disease effect.

Butrin is a compound found in Butea monosperma flowers. Butrin reduces expression of SIRT1, AURKB, cyclin D1, pAKT, GSK-3β, β-catenin, and TGF-3β expression, enhances apoptosis and ROS production in cancer cells. Butrin downregulates Wnt and NF-κB signaling, mitigates oxidative stress, reduces proinflammatory cytokine (TNF-α, IL-6 and IL-8) production and suppresses neuroinflammation. Butrin inhibits IKK enzyme activity. Butrin can be used for the researches of colorectal cancer, Alzheimer’s disease, and rheumatoid arthritis.

Aloisine RP106 (compound 38) is a potent inhibitor of Cdk1/cyclin B, Cdk5/p25, and GSK3 with IC₅₀s of 0.70µM, 1.5µM, 0.92 µM, respectively.

Indirubin-5-sulfonate is a cyclin-dependent kinase (CDK) inhibitor, with IC₅₀ values of 55 nM, 35 nM, 150 nM, 300 nM and 65 nM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK4/cyclin D1, and CDK5/p35, respectively. Indirubin-5-sulfonate also shows inhibitory activity against GSK-3β.

BI-5521 is an orally active GSK-3 inhibitor with an IC₅₀ of 1.1 nM against GSK-3β. BI-5521 targets the two GSK-3 isoforms with similar potency and exhibits potent inhibitory activity against DYRK1A. By modulating GSK-3 activity, BI-5521 inhibits tumor proliferation and cancer cell growth, exerts cytotoxic effects, and reduces cancer cell viability. It shows consistent chemosensitivity across all subtypes of rhabdomyosarcoma, produces synergistic growth inhibitory effects when combined with SOS1 inhibitors, reduces oral glucose levels, regulates the myofibroblast differentiation pathway, decreases the nuclear localization of YAP/SMAD2/3, and lowers the positive rate of α-SMA in fibroblasts without affecting the apoptosis of CD4⁺ T cells. BI-5521 can be used in the research of non-small cell lung cancer, pleomorphic rhabdomyosarcoma, type 2 diabetes, pancreatic ductal adenocarcinoma, Alzheimer's disease, bipolar disorder, and metabolic dysfunction-associated steatotic liver disease.

RR-171 is an amino acid polypeptide and an inhibitor of the Wnt signaling pathway. RR-171 reduces the expression levels of Wnt-1, GSK3β and β-catenin. RR-171 induces apoptosis (Apoptosis) in pancreatic cancer cells, which is characterized by an increased Bax/Bcl-2 ratio, activation of Caspase-3/7/9, and increased Cleaved-PARP; this pro-apoptotic effect can be partially reversed by Z-VAD-FMK (HY-16658B). RR-171 also induces pyroptosis (Pyroptosis) in pancreatic cancer cells, which is manifested by activation of the NLRP-3 inflammasome, activation of Caspase-1, cleavage of GSDMD, upregulation of IL-1β and IL-18, and increased LDH release; this pro-pyroptotic effect can be partially reversed by VX-765 (HY-13205). RR-171 inhibits the viability, proliferation and colony formation of pancreatic cancer cells, with low cytotoxicity against normal cells. RR-171 downregulates the expression of Ki-67 and PCNA in tumor tissues in vivo, with favorable biosafety. RR-171 can be used in studies related to pancreatic cancer.

GSK-3β-IN-31 is a glycogen synthase kinase-3β (GSK-3β) inhibitor. GSK-3β-IN-31 binds to the ATP-binding pocket of GSK-3β, forms hydrogen bonds with Lys183 and Ser203, and also engages in π-anion interactions with Asp181 and Asp200 to stabilize the binding conformation. GSK-3β-IN-31 can be used for the research of Alzheimer's disease.

PfGSK3/PfPK6-IN-2 is a potent dual PfGSK3/PfPK6 (Plasmodium falciparum GSK3/PK6) inhibitor (IC₅₀: 172 nM and 11 nM respectively). PfGSK3/PfPK6-IN-2 can be used in the research of Malaria.

GSK-3β inhibitor 14 (Compound 6i), benzothiazepinone derivative, is a weak GSK-3β inhibitor (IC₅₀ >100 μM).

ZDWX-25 is a highly potent GSK-3β and DYRK1A dual inhibitor with an IC₅₀ value of 71 nM for GSK-3β. ZDWX-25 possesses significant cytotoxic activities against SH-SY5Y and HL-7702 cells. ZDWX-25 can be used for researching alzheimer's disease.

GSK-3β/VEGFR2-IN-1 is an orally active dual inhibitor of GSK-3β (IC₅₀ = 325 nM) and VEGFR2 (IC₅₀ = 78 nM). GSK-3β/VEGFR2-IN-1 suppresses the phosphorylation of VEGFR2, AKT, MEK and ERK, inhibits human tongue squamous cell carcinoma cells migration and suppresses formation of HUVECs, exhibits low toxicity towards other cancer cells and normal cells, demonstrates significant antitumor efficacy in a CAL27 xenograft mouse model. GSK-3β/VEGFR2-IN-1 can be used for the study of tongue squamous cell carcinoma.

GSK-3β inhibitor 18 (compound 2) is a potent inhibitor of GSK-3β, with the IC₅₀ of 0.0021 μM.

JNK3 inhibitor-9 (Compound 24a) is a potent, selective and BBB-permeable JNK3 inhibitor with an IC₅₀ value of 12 nM. JNK3 inhibitor-9 also potently inhibits GSK3α/β (IC₅₀s: 14 and 35 nM, respectively) involved in Tau phosphorylation. JNK3 inhibitor-9 reduces c-Jun and APP phosphorylation. JNK3 inhibitor-9 protects neurons from Aβ_1-42 toxicity.

MLS-2064 is a 3'-substituted 7-haloindirubin with antitumor activity. MLS-2064 induces caspase-independent cell death. MLS-2064 induces dose-dependent cell death in various human cancer cell lines. MLS-2064 shows no significant inhibitory activity against CDK1 and CDK5 kinases, and only weak inhibitory activity against GSK-3 kinase (IC₅₀: 5 μM). MLS-2064 can be used in research related to colon cancer, breast cancer, lung cancer, prostate cancer, liver cancer, and neuroblastoma.