CHIR-99021 , ≥98% , 252917-06-9

Synonym(s):
6-(2-(4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)-pyrimidin-2-ylamino)ethyl-amino)-nicotinonitrile;6-[[2-[[4-(2,4-Dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)-2-pyrimidinyl]amino]ethyl]amino]-3-pyridinecarbonitrile

CAS NO.：252917-06-9

Empirical Formula: C22H18Cl2N8

Molecular Weight: 465.34

MDL number: MFCD11846251

EINECS: 809-015-4

PRODUCT Properties

• Boiling point: 784.1±70.0 °C(Predicted)
• Density: 1.48
• storage temp.: -20°C
• solubility: DMSO: soluble2mg/mL, clear (warmed)
• pka: 11.92±0.10(Predicted)
• form: powder
• color: white to light brown
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• InChIKey: AQGNHMOJWBZFQQ-UHFFFAOYSA-N
• SMILES: C1=NC(NCCNC2=NC=C(C3NC(C)=CN=3)C(C3=CC=C(Cl)C=C3Cl)=N2)=CC=C1C#N
• CAS DataBase Reference: 252917-06-9

Description and Uses

CHIR99021 is an aminopyrimidine derivative that is an extremely potent glycogen synthase kinase (GSK) 3 inhibitor, inhibiting both GSK3β (IC?? = 6.7 nM) and GSK3α (IC?? = 10 nM). GSK3 is a serine/threonine kinase that is a key inhibitor of the WNT pathway; therefore CHIR99021 functions as a WNT activator. It shows little activity against a large panel of kinases including CDK2 and other serine/threonine kinases such as MAPK and PKB (Bain et al.).
CHIR99021 promotes self-renewal potential of embryonic stem cells (ESCs) of mice by inhibiting glycogen synthase kinase-3 (GSK-3) activity and potentiates the upregulation of β-catenin and c-Myc functions. CHIR99021 promotes self-renewal of ESCs by modulating transforming growth factor β (TGF-β), Notch and mitogen-activated protein kinases (MAPK) signaling pathways. CHIR99021 is an agonist of wingless/integrated (wnt) signalling, upregulates cyclinA expression and promotes cell proliferation in non-small-cell lung cancer (NSCLC) cell lines.

Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that plays a key inhibitory role in both the insulin and Wnt signaling pathways. CHIR99021 is an aminopyrimidine derivative that inhibits GSK3α and GSK3β with IC50 values of 10 and 6.7 nM, respectively. When tested against twenty different protein kinases, this inhibitor shows greater than 500-fold selectivity for GSK3. CHIR99021 activates glycogen synthesis in CHO-IR cells (EC50 = 0.8 μM) and in isolated type 1 diabetic rat skeletal muscle. A single oral dose (30 mg/kg) of CHIR99021 enhances in vivo glucose metabolism in a rodent model of type 2 diabetes. CHIR99021 has also been shown to induce the reprogramming of murine and human somatic cells into stem cells.

Safety

• Symbol(GHS): GHS06
• Signal word: Danger
• Hazard statements: H300-H315-H319-H335
• Precautionary statements: P261-P264-P301+P310-P305+P351+P338
• Hazard Codes: T
• Risk Statements: 25-36/37/38
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• HS Code: 29335990