CHIR-98014 - Moligand™, 10mM in DMSO , Inhibitor of glycogen synthase kinase 3 alpha;Inhibitor of glycogen synthase kinase 3 beta, CAS No.252935-94-7, Inhibitor of glycogen synthase kinase 3 alpha;Inhibitor of glycogen synthase kinase 3 beta

CAS: 252935-94-7 Cat. No.: C408890 Peso molecular: 486.31

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

CT98014 | N2-(2-(4-(2,4-dichlorophenyl)-5-(1H-imidazol-1-yl)pyrimidin-2-ylamino)ethyl)-5-nitropyridine-2,6-diamine

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

CHIR-98014 (CT98014) is a potentGSK-3α/βinhibitor withIC50of 0.65 nM/0.58 nM in cell-free assays, with the ability to distinguish GSK-3 from its closest homologs Cdc2 and ERK2.
In vitro

CHIR-98014 inhibits human GSK-3β with K_i of 0.87 nM. CHIR-98014 is very effective in preventing murine and rat GSK-3. Although CHIR-98014 acts as a simple competitive inhibitor of ATP binding, it displays from 500-fold to >1000-fold selectivity for GSK-3 versus 20 other protein kinases including Cdc2, ERK2, Tie-2 and KDR. CHIR-98014 prevents Cdc2 with IC50 of 3.7 μM. However, CHIR 98014 reveals similar ptoency against the highly homologous ɑ and β isoforms of GSK-3, it is noteworthy that it stronly discriminated between GSK-3 and its closest homologs CDC2 and ERK2. Exposure of insulin receptor-expressing CHO-IR cells or primary rat hepatocytes to increasing concentrations of inhibitor CHIR98014 results in a two- to three-fold stimulation of the GS activity ratio above basal. The concentrations of CHIR-98014 giving rise to half-maximal GS stimulation (EC50) is 106 nM and 107 nM for CHO-IR and rat hepatocytes, respectively.

In vivo

GSK-3 inhibitor CHIR-98014 activates the GS activity ratio in isolated type I skeletal muscle from insulin-sensitive lean Zucker and from insulin-ressitant ZDF rats. Soleus muscle isolated from ZDF rats shows significant resistance to insulin for activation of GS but responded to 500 nM CHIR-98014 to the same extent (40% increase) as muscle from lean Zucker rats. Notably, GS activation by insulin plus CHIR-98014 is additive in muscle from lean Zucker rats and greater than additive in muscle from the ZDF rats. Total GS activity is not altered by either CHIR-98014 or insulin in these cells and muscles. Meanwhile, CHIR-98014 does not influence the insulin dose-response in muscle from lean animals. The reduction in hyperglycemia and improved glucose disposal are not limited to db/db mice and ZDF rats, as similar results are observed with ob/ob mice, diet-induced diabetic C57BL/6 mice, and glucose-intolerant SHHF rats treated with CHIR-98014. Additionally, CHIR-98014 decreases the phosphorylation (Ser396) of tau protein in the cortex and hippocampus of postnatal rats.
Cell Data

cell lines：

Concentrations：0.01-10 μM

Incubation Time：30 min

Powder Purity:≥99%

Specifications

Sinónimos

CT98014 | N2-(2-(4-(2, 4-dichlorophenyl)-5-(1H-imidazol-1-yl)pyrimidin-2-ylamino)ethyl)-5-nitropyridine-2, 6-diamine

Especificaciones y pureza

Moligand™, 10mM in DMSO

Mecanismos bioquímicos y fisiológicos

CHIR-98014 (CT98014) is a potent GSK-3α/β inhibitor with IC50 of 0.65 nM/0.58 nM in cell-free assays, with the ability to distinguish GSK-3 from its closest homologs Cdc2 and ERK2.

Condiciones de almacenamiento de almacenamiento

Store at -80°C

Enviado en

Dry ice packs + Cold packs

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Grado

Moligand™

Tipo de acción

INHIBITOR

Mecanismo de acción

Inhibitor of glycogen synthase kinase 3 alpha;Inhibitor of glycogen synthase kinase 3 beta

Nombres e identificadores

• Isómeros SMILES: C1=CC(=C(C=C1Cl)Cl)C2=NC(=NC=C2N3C=CN=C3)NCCNC4=NC(=C(C=C4)[N+](=O)[O-])N
• WGK Alemania: 3
• Peso molecular: 486.31
• Reaxy-Rn: 13937684
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=13937684&ln=

Objetivos asociados (humanos)

GSK3B Tclin Glycogen synthase kinase-3 beta (2 Activities)

Discover Target: GSK3B

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

GSK3A Tclin Glycogen synthase kinase-3 alpha (2 Activities)

Discover Target: GSK3A

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Propiedades químicas y físicas

• Solubilidad: Solubility (25°C) In vitro DMSO: 100 mg/mL (434.21 mM)