GSK-3

CHIR-99021 (CT99021) is an activator of the Wnt/β-catenin signaling pathway and a GSK-3α/β inhibitor (IC50=10/6.7 nM) with selective and oral activity.CHIR-99021 induces cellular autophagy, which enhances self-renewal in mouse and human embryonic stem cells.

GNF4877 is a potent inhibitor of DYRK1A and GSK3β (IC50s: 6 nM and 16 nM, respectively), resulting in the blockade of nuclear export of nuclear factor of activated T-cells (NFATc) and increased β-cell proliferation.

(-)-Agelastatin A is a member of the pyrrole-aminoimidazole marine alkaloid (PAI) family, capable of inhibiting β-catenin, GSK-3β, and osteopontin (OPN), exhibiting antiproliferative activity against various cancers such as leukaemia and breast cancer, and possessing a certain ability to penetrate the central nervous system (CNS).

CHIR-99021 HCl (Laduviglusib HCl) is a highly potent and selective inhibitor of GSK-3α/β, with IC50 values of 10 nM and 6.7 nM respectively. It demonstrates remarkable selectivity for GSK-3, with over 500-fold selectivity over CDC2, ERK2, and other protein kinases. Additionally, CHIR-99021 HCl serves as a robust activator of the Wnt/β-catenin signaling pathway. Moreover, it exhibits the ability to enhance self-renewal in both mouse and human embryonic stem cells. Furthermore, CHIR-99021 HCl induces autophagy [1] [2] [3].

Tideglusib (NP031112), a non-ATP competitive inhibitor of glycogen synthase kinase 3 (GSK-3), is with anti-inflammatory and neuroprotective activities.

1. Resibufogenin (Bufogenin) is a cytotoxic steroid isolated from the Chinese drug ChanSu. 2. Resibufogenin can inhibit rectifier potassium current ( I K ) and transient potassium current ( I A ), it has pathological effects on central nervous system. 3. Resibufogenin corrects hypertension in a rat model of human preeclampsia, it not only prevents the advent of hypertension and proteinuria, but also the development of intrauterine growth restriction.4. Resibufogenina's major metabolic pathway in the human liver is CYP3A4 dominantly mediated 5β-hydroxylation .

Laduviglusib trihydrochloride (CT99021 trihydrochloride) is a selective glycogen synthase kinase 3 (GSK-3) inhibitor with IC50s of 10 nM and 6.7 nM for GSK-3α and GSK-3β. Laduviglusib trihydrochloride inhibits human GSK-3β with a Ki of 9.8 nM. Laduviglusib trihydrochloride is an activator of Wnt/β-catenin signaling. Laduviglusib trihydrochloride induces autophagy.

Alpha-Amyrin (alpha-Amyrine) is an inhibitor of trypsin and chymotrypsin with antineoplastic effects. alpha-Amyrin can be used in studies about acting as a hepatomodulatory.

MBM-55S is an effective inhibitor of Nek2 with an IC50 of 1 nM. MBM-55S indecus cell cycle arrest and apoptosis thereby inhibiting the proliferation of cancer cells. MBM-55S shows antitumor activities.

Moringin is an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucoMoringin present in Moringa oleifera seeds. Moringin has anti-inflammatory and antioxidative properties.

Eupalinolide A has the effects of relieving phlegm and relieving cough, clearing away heat and detoxification, diuretic swelling and reducing blood pressure.

AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor.

LY2090314, an effective GSK-3α/β inhibitor (IC50: 1.5 nM/0.9 nM), may improve the efficacy of platinum-based chemotherapy regimens. LY2090314 has been used in trials studying the treatment of Leukemia, Advanced Cancer, and Pancreatic Cancer.

EHT 1610 (EHT 5372) is a potent inhibitor of DYRK, with an IC50 of 0.36 nM and 0.59 nM for DYRK1A and DYRK1B, respectively. EHT 1610 has an inhibitory effect on leukemia, regulating cell cycle and inducing cell apoptosis.

1. Levistolide A (Diligustilide) inhibits liver fibrosis and angiogenesis.

KY19382 (2H-Indol-2-one, 5,6-dichloro-3-[1,3-dihydro-3-(methoxyimino)-2H-indol-2-ylidene]-1,3-dihydro-Ky19382) is a potent and orally active dual inhibitor of CXXC5-DVL and GSK3β( IC50s of 19 and 10 nM, respectively). It activates Wnt/β-catenin signaling through inhibitory effects on both CXXC5-DVL interaction and GSK3β activity. KY19382 can be used for the research of high fat diet (HFD) induced metabolic diseases.

kaempferide (4'-Methylkaempferol) inhibits the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation.

GSK-3 inhibitor 4 is an orally active and brain-permeable compound that acts as a triple inhibitor of GSK-3, CDK2, and CDK5, with IC50 values of 0.56 nM (GSK-3β), 0.45 nM (GSK-3α), 0.47 μM (CDK2), and 0.68 μM (CDK5). It effectively reduces Tau protein levels and can be used in the study of Alzheimer's disease.

SNS-032 (BMS-387032) is a selective inhibitor of CDK2 (IC50: 48 nM), exhibiting 10- and 20-fold selectivity over CDK1 and CDK4, respectively. It is also sensitive to CDK7 (IC50: 62 nM) and CDK9 (IC50: 4 nM), with no effect on CDK6.

Bisindolylmaleimide I (GF109203X) is a potent and highly selective protein kinase C (PKC) inhibitor, exhibiting a Ki of 14 nM.

HTH-01-091 is a potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor (IC50: 10.5 nM) that also inhibits PIM1/2/3, RIPK2, DYRK3, smMLCK, and CLK2. It can be used to study breast cancer.

BRD0705 is a potent, orally active GSK3α inhibitor with high selectivity (IC50: 66 nM; Kd: 4.8 μM), demonstrating an 8-fold higher selectivity for GSK3α compared to GSK3β (IC50: 515 nM).

1. Kuwanon G (Moracenin B) as dual inhibitors of PTP1B and α-glucosidase enzymes, as well as insulin sensitizers, it may potentially be utilized as an effective treatment for Type II diabetes mellitus. 2. Kuwanon G has anti-inflammatory activity, it can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response. 3. Kuwanon G is a potent inhibitor of Mycobacterium tuberculosis protein tyrosine phosphatase B. 4. Kuwanon G shows acetylcholinesterase (AChE) and butyrylcholinesterase(BChE) inhibitory activities, it may be a promising candidate for preventive and therapeutic agents for Alzheimer's disease. 5. Kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. 6. Kuwanon G has antibacterial activity against oral pathogens. 7. Kuwanon G is a specific antagonist for the GRP-preferring receptor and can be useful for studying the physiological and pathological role of GRP.

(Rac)-BRD0705, the less active racemate of BRD0705, is an effective and selective inhibitor of GSK3α.