|This article, CHIR99021, was written by RelentlessRecusant. Please do not edit this fiction without the writer's permission.|
CHIR99021, IUPAC name 6-(2-(4-(2,4-dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino)ethylamino)nicotinonitrile, is a small-molecule chemical inhibitor of glycogen synthase kinase 3β (GSK3β), and is highly selective, showing nearly thousandfold selectivity against a panel of related and unrelated kinases, with an IC50 = 6.7 nM against human GSK3β and nanomolar IC50 values against rodent GSK3β homologs.
CHIR99021 has been found to have both clinical and experimental utility; it induces insulin-responsive glucose uptake in insulin-resistant murine hepatocytes, and thus has extensive implications in the induction of hypoglycemia and the acute treatment of symptoms of the diabetic pathological phenotype. It has been previously demonstrated that other GSK3β inhibitors, specifically BIO-Acetoxime, activate the Wnt signaling pathway in human and murine embryonic stem (ES) cells, and CHIR99021 has indeed been shown to allow for long-term expansion of murine embryonic stem cells in a chemically-defined medium in conjunction with MEK/MAPK inhibitor PD184352 and fibroblast growth factor receptor (FGFR) inhibitor SU5402.
- ↑ 1.0 1.1 Ring et. al (2003). Selective Glycogen Synthase Kinase 3 Inhibitors Potentiate Insulin Activation of Glucose Transport and Utilization In Vitro and In Vivo. Diabetes (52): 588–595.
- ↑ Sato et. al (2004). Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nature Medicine (10): 55-63.
- ↑ Ying et. al (2008). The ground state of embryonic stem cell self-renewal. Nature (453): 519-524
|Chemical Biology: Small-Molecule Control of Biological Systems (RelentlessRecusant)|
|Receptor Tyrosine Kinases||A-83-01 (TGFβ/Activin) · BPIQ-II (EGFR) · Dorsomorphin/LDN-193189 (TGFβ/BMP) · SU5402 (FGFR)|
|Signaling Kinases||A-769662 (AMPK) · BMS-354825 (BCR-ABL, Src)· BIO-Acetoxime (GSK3) · CHIR99021 (GSK3) · GO 6976 (PKC) · IMD-0354 (IκBa) · PD184352 (MAPK) · SB203580 (MAPK) · Y-27632 (ROCK)|
|G Protein-Coupled Receptor||(R)-(+)-WIN 55212 (CB1/CB2) · ±-Sulpride (D2) · A 841720 (mGluR1) · BP-554 (5-HT1A) · Hh-Ag1.5 (Smo) · Cyclopamine/KAAD-Cyclopamine (Smo) · SANT1 (Smo) · SB-277011 (D3)|
|Ion Channels||BAY K8644 (Cav1.2) · Bicuculline (GABAAR) · Cymarin (Na+/H+) · G-strophanthin (Na+/H+) · L-AP4 (Na+/H+) · Oxcarbazepine (Na+) · Resiniferatoxin (TRPV1) · Sarmentogenin (Na+/H+) · Theanine (AMPAR, NMDAR)|
|Transporters||O-1783 (DAT) · WF-23 (DAT, SERT)|
|Nuclear Receptor||All-trans retinoic acid (RAR/RXR) · GW501516 (PPARδ) · RU-486 (Nr3c1, Nr3c3)|
|Protein Phosphatases||Endothall (PP2A)|
|Polypharmacological||Phosphoserine (mGluR4) · PK115-584 (Tcf4/β-catenin, PKC) · Pluripotin · Reversine|
|Other||2C-E (DAT) · 4-methoxyphenyl-HTI-286 (α/β-tubulin) · Compound E/DAPT (presenilin-1) · D-cysteine · D-phenylalanine · Flurbiprofen (COX) · JZL184 (MAGL) · QS11 (RAFGAP1) · RO-28-1675 (glucokinase) · Robotnikinin (Shh) · Selegiline (MAOB)|
|Libraries||Kinase Inhibitor Library|
|Small molecule-mediated manipulation of the adult human induces selective and reversible control of physiological and psychological phenotype (Rubin et. al, 2590. Nature Medicine)|
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