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CHIR99021

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40px-Terminal.png This article, CHIR99021, was written by RelentlessRecusant. Please do not edit this fiction without the writer's permission.
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CHIR99021

The chemical structure of CHIR99021.

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.[1]

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.[1] 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[2], 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.[3]

References

  1. 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.
  2. 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.
  3. 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)
Compound Names (Biological Targets)
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)
Uncharacterized Neuropathiazol
Libraries Kinase Inhibitor Library
Publications
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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