[CAS NO. 252935-94-7] CHIR-98014

Name: CHIR-98014
Brand: Arctom Scientific
SKU: SLK-S2745

Ships within

Stock

Price

Qty

Total

$0.00

Please click "REQUEST A QUOTE" button if you need other sizes or custom synthesis

request a quote

If there is no stock, or you need other sizes or custom synthesis, please:

PRODUCTS SPECIFICATIONS [252935-94-7]

Store

Catalog

SLK-S2745

Brand

Selleck

CAS

252935-94-7

DESCRIPTION [252935-94-7]

Overview

MDL	MFCD10565922
Molecular Weight	486.31
Molecular Formula	C20H17Cl2N9O2
SMILES	ClC1=C(C=2C(=CN=C(NCCNC=3N=C(N)C(N(=O)=O)=CC3)N2)N4C=CN=C4)C=CC(Cl)=C1

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Concentration Volume Mass	1 mg	5 mg	10 mg
1 mM	2.0563 mL	10.2815 mL	20.5630 mL
5 mM	0.4113 mL	2.0563 mL	4.1126 mL
10 mM	0.2056 mL	1.0282 mL	2.0563 mL
50 mM	-	-	-

Description

CHIR-98014 (CT98014) is a potent inhibitor with 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.

Targets

GSK-3β ^[1] (Cell-free assay)	GSK-3α ^[1] (Cell-free assay)
0.58 nM	0.65 nM

In vitro

CHIR-98014 inhibits human GSK-3β with K 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.

References

[1] Ring DB,et al. Diabetes. 2003, 52(3), 588-595.
[2] Selenica ML, et al. Br J Pharmacol. 2007, 152(6), 959-979.

Synonyms

2,6-Pyridinediamine, N⁶-[2-[[4-(2,4-dichlorophenyl)-5-(1H-imidazol-1-yl)-2-pyrimidinyl]amino]ethyl]-3-nitro-

N⁶-[2-[[4-(2,4-Dichlorophenyl)-5-(1H-imidazol-1-yl)-2-pyrimidinyl]amino]ethyl]-3-nitro-2,6-pyridinediamine

CHIR 98014

CT 98014