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[1].
Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC50s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC50=0.5 µM) and GSK-3β (IC50=1.5 µM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research[1][2].
Antitrypanosomal agent 14 (Compound 1) is a T. brucei inhibitor (EC50: 0.47 μM). Antitrypanosomal agent 14 inhibits TbGSK3 with an IC50 of 12 μM. Antitrypanosomal agent 14 can be used for the research of Human African trypanosomiasis[1].
GSK-3β inhibitor 14 (Compound 6i), benzothiazepinone derivative, is a weak GSK-3β inhibitor (IC50 >100 μM)[1].
GSK2646264 (Compound 44) is a potent and selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.1. GSK2646264 also inhibits other kinases with pIC50 values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3 against LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B and Aurora A, respectively. GSK2646264 is penetrable into the epidermis and dermis of the skin[1].
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-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC50s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC50=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease[1].
TCS 21311 (NIBR3049) is a potent, highly selective JAK3 inhibitor with an IC50 of 8 nM, it displays >100-fold selectivity over JAK1, JAK2 and TYK2. TCS 21311 (NIBR3049) inhibits PKCα, PKCθ, and GSK3β with IC50s of 13, 68, and 3 nM, respectively[1].
A potent, highly selective GSK-3 inhibitor with IC50 of 2.1 nM for human GSK-3β in enzyme assays; shows equal effectivity against GSK-3α and GSK-3β with IC50 of 10.0 and 9.0 nM respectively in mobility shift assays, inhibits phosphorylation of tau with an IC50 of 466 nM in a stable inducible CHO cell line over-expressing GSK-3β and substrate tau; modulates tau phosphorylation in vitro and in vivo.
CHIR-98014 is a potent, cell-permeable GSK-3 inhibitor with IC50s of 0.65 and 0.58 nM for GSK-3α and GSK-3β, respectively; it shows less potent activities against cdc2 and erk2.
hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC50 of 0.11 nM. hSMG-1 inhibitor 11j exhibits >455-fold selectivity for hSMG-1 over mTOR (IC50=50 nM), PI3Kα/γ (IC50=92/60 nM) and CDK1/CDK2 (IC50=32/7.1 μM). hSMG-1 inhibitor 11j can be used for the research of cancer[1].
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[1][2][3].
MeBIO is a potent AhR (aryl hydrocarbon receptor) agonist, with IC50 of 44 μM (GSK-3) and 55 μM (CDK1/cyclin B), respectively. MeBIO is inactive on GSK-3β[1].
Lithium chloride hydrate, an orally active mood stabilizer, is a potent virus inhibitor and effective immunomodulatory agent. Lithium chloride hydrate has antidepressant activity by inhibiting GSK3β and promoting neurogenesis. Lithium chloride hydrate alleviates cognition dysfunction and the symptoms of acute mania and depression. Lithium chloride hydrate can also be used for research of virus infection and Alzheimer's disease[1][2][3].
GSK3-IN-3 is a mitophagy inducer, inducing Parkin-dependent mitophagy. GSK3-IN-3 is also a GSK-3 inhibitor with an IC50 value of 3.01 μM. GSK3-IN-3 is non-ATP nor substrate competitive and is neuroprotective against 6-OHDA[1][2][3].
GSK-3β inhibitor 10 (compound 14a) is a highly potent GSK-3β inhibitor with an IC50 value of 80.5 nM. GSK-3β inhibitor 10 can be used for researching Alzheimer’s disease[1].
AChE/GSK-3β-IN-1 (compound GT15) is a potent, dual AChE/GSK-3β inhibitor with IC50 values of 1.2, 149.8 and 22.4 nM for hAChE , hBChE and hGSK-3β, respectively. AChE/GSK-3β-IN-1 penetrates the blood-brain barrier (BBB). AChE/GSK-3β-IN-1 has high kinase selectivity profiles for the CMGC kinase family. AChE/GSK-3β-IN-1 occupies the ATP binding site of DYRK1A. AChE/GSK-3β-IN-1 inhibits ROS expression and reduces oxidative stress. AChE/GSK-3β-IN-1 can be used for Alzheimer’s disease research[1].
HTH-01-091 is a potent and selective, cell-permeable, ATP-competitive MELK inhibitor with biochemical IC50 of 10.5 nM; displays no significant activity for PIK3CA, mTOR, GSK3A and CDK7 (IC50>600 nM); exhibits substantially improved kinome selectivity in comparison with OTSSP167; induces MELK degradation, but demonstrates poor antiproliferative effects in basal-like breast cancer cell lines.
GNF4877 is a potent DYRK1A and GSK3β inhibitor with IC50s of 6 nM and 16 nM, respectively, which leads to blockade of nuclear factor of activated T-cells (NFATc) nuclear export and increased β-cell proliferation (EC50 of 0.66 μM for mouse β (R7T1) cells)[1].
CDK8-IN-12 is an orally active, potent CDK8 inhibitor with a Ki of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with Kis of 13 nM, 4 nM, 109 nM, respectively. CDK8-IN-12 shows potent anti-proliferative effects selectively on MV4-11 cell. CDK8-IN-12 is an anti-cancer agent[1].
ABC1183 is a potent, selective, orally active GSK3α/β and CDK9 inhibitor with IC50 of 327/657 nM and 321 nM (CDK9/cyclin T1), shows growth inhibitory activity against a broad panel of cancer cell lines; decreases cell survival through G2/M arrest and modulates oncogenic signaling through changes in GSK3, GS and β-catenin phosphorylation and MCL1 expression; suppresses tumor growth and inflammation-driven gastrointestinal disease symptoms without organ or hematological toxicity in vivo.
GSK3-IN-4 (compound 0715) is a potent GSK3 inhibitor. GSK3-IN-4 can be used for psychiatric disorder research[1].
BRD0705 (BRD-0705) is a potent, paralog-selective GSK3α inhibitor with IC50 of 66 nM, 8-fold selectivity over GSK3β (IC50=515 nM); displays excellent selectivity in a penal of 311 kinases, the CDK family of CDK2, CDK3 and CDK5) are most potently inhibited with IC50 of 6.87, 9.74 and 9.20 uM (87-, 123-, and 116-fold selectivity relative to GSK3α); inhibits GSK3α kinase function, impairs GSK3α Tyr279 phosphorylation in a time- and concentration-dependent manner without affecting GSK3β Tyr216 phosphorylation, and does not stabilize β-catenin, induces myeloid differentiation and impairs colony formation in AML cells, with no apparent effect on normal hematopoietic cells; impairs leukemia initiation and prolongs survival in AML mouse models.
GSK-3 inhibitor 3 is a selective, orally active and brain-penetrant inhibitor of GSK-3, with IC50s of 0.35 nM and 0.25 nM for GSK-3α and GSK-3β, respectively. GSK-3 inhibitor 3 lowers levels of tau protein phosphorylation at S396 in a triple-transgenic mouse Alzheimer’s disease model, with IC50 of 10 nM. GSK-3 inhibitor 3 can be used for neurological disease research[1].
GS87 is a highly specific and potent GSK3 inhibitor with IC50s of 415nM and 521nM for GSK3α and GSK3β, respectively. GS87 induces differentiation of acute myeloid leukemia (AML) cell lines by effectively activating GSK3-dependent signaling components including MAPK signaling. GS87 modulates key GSK3 target proteins involved in cell proliferation and differentiation more effectively than Lithium and SB415285 (SB). GS87 has the potential for acting as a differentiation agent for non-promyelocytic AML research[1].
GSK-3β inhibitor 8, a thiophenacil derivative, is an effective and selective inhibitor of GSK-3β (IC50=64 nM). GSK-3β inhibitor 8 negatively regulated Wnt signaling pathway and stimulated β cell proliferation[1][2].
BIO-acetoxime (BIA) is a potent and selective GSK-3 inhibitor, with IC50s of both 10 nM for GSK-3α/β. BIO-acetoxime has anticonvulsant and anti-infection activity.
TDZD-8 is an inhibitor of GSK-3β, with an IC50 of 2 μM; TDZD-8 shows less potent activities against Cdk-1/cyclin B, CK-II, PKA, and PKC, with all IC50s of >100 μM.
A 1070722 is a potent and selective glycogen synthase kinase 3 (GSK-3) inhibitor, with a Ki 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[1].
GSK-3β inhibitor 12 (compound 15) is an inhibitor of GSK-3β. GSK-3β inhibitor 12 inhibits 49.11% and 37.11% activity of 25 μM and 50 μM GSK-3β, respectively. GSK-3β inhibitor 12 can be used for the research of neurodegenerative diseases[1].