CHIR99021

Описание

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.

Использование

A specific GSK-3 inhibitor of GSK-3β and GSK-3α with IC50s of 5 nM and 10 nM, respectively.

прикладной

CHIR 99021 is an aminopyrimidine derivate that is a selective and potent inhibitor of glycogen synthase kinase 3 (GSK-3). It is used to maintain human and mouse stem cell lines and, in combination with other reagents, to chemically reprogram somatic cells into stem cells.
CHIR99021 has been used:
in cocktail with small molecules to convert human lung fibroblast cells into neurons
as a culture medium supplement in potassium supplemented simplex optimization medium (KSOM)
for the culture of blastocysts for chronic inhibition of GSK-3 to investigate its role in corticogenesis

Определение

ChEBI: A member of the class of aminopyrimidines that is 2-aminopyrimidine substituted at positions N2, 5 and 6 by (5-cyanopyridin-2-yl)ethyl, 4-methylimidazol-2-yl and 2,4-dichlorophenyl groups respectively.

Общее описание

CHIR99021 is an aminopyrimidine derivative. 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.

Биологическая активность

CHIR 99021 is a potent and highly selective inhibitor of glycogen synthase kinase 3 (GSK-3) (IC50 values are 6.7 and 10 nM for GSK-3β and GSK-3α respectively). Acts as Wnt activator. Exhibits >500-fold selectivity for GSK-3 over closely related kinases; also displays >800-fold selectivity against 45 additional enzymes and receptors. In combination with the irreversible inhibitor of LSD1 (Cat. No. 3852), CHIR 99021 enables reprogramming of mouse embryonic fibroblasts, transduced by Oct4 and Klf4 only, into iPSCs. CHIR 99021 enhances mouse and human ESC self-renewal when used in combination with PD 0325901 (Cat. No. 4192). CHIR 99021 allows formation of extended pluripotent stem (EPS) cells in combination with (S)-(+)-Dimethindene maleate (Cat.No. 1425), tetracycline antibiotic (Cat.No. 3268) and human leukemia inhibitory factor.