252917-06-9

Basic information

• Product Name: 6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile
• Synonyms: 6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile;6-{2-[4-(2,4-Dichloro-phenyl)-5-(4-methyl-1H-imidazol-2-yl)-pyrimidin-2-ylamino]-ethylamino}-nicotinonitrile;CHIR-99021;CT99021;GSK-3 Inhibitor XVI;3-Pyridinecarbonitrile, 6-[[2-[[4-(2,4-dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)-2-pyrimidinyl]amino]ethyl]amino];CT 99021(CHIR 99021);6-[2-[4-(2,4-Dichlorophenyl)-5-(4-Methyl-1H-iMidazol-2-yl)pyriMidin-2-ylaMino]ethylaMino]pyridine-3-
• CAS NO: 252917-06-9
• Molecular Formula: C22H18Cl2N8
• Molecular Weight: 465.35
• EINECS: 1312995-182-4
• Product Categories: Antineoplastic;Anti-cancer&immunity;PI3K/Akt/mTOR;Inhibitors;Akt;mTOR;PI3K
• Mol File: 252917-06-9.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 784.08 °C at 760 mmHg
• Flash Point: 427.996 °C
• Appearance: white to light brown/
• Density: 1.48
• Storage Temp.: ?20°C
• Solubility: DMSO: soluble2mg/mL, clear (warmed)
• PKA: 11.92±0.10(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: 6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile(252917-06-9)
• EPA Substance Registry System: 6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile(252917-06-9)

Safety Data

• Hazard Codes: T
• Statements: 25-36/37/38
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 252917-06-9(Hazardous Substances Data)

Usage

Description

6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile is an aminopyrimidine derivative with a complex chemical structure, featuring various functional groups such as a 2,4-dichlorophenyl, a 4-methylimidazol-2-yl, and a 5-cyanopyridin-2-ylethyl group.

Uses

Used in Pharmaceutical Applications:
6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile is used as a potent inhibitor of glycogen synthase kinase 3 (GSK-3) for its role in various cellular processes and signaling pathways.
Used in Stem Cell Research:
In the field of stem cell research, 6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile is used to maintain human and mouse stem cell lines and, in combination with other reagents, to chemically reprogram somatic cells into stem cells.
Used in Neuroscience:
6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile is used in cocktail with small molecules to convert human lung fibroblast cells into neurons, contributing to the understanding of neuronal development and potential therapeutic applications.
Used in Developmental Biology:
In developmental biology, 6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile serves as a culture medium supplement in potassium supplemented simplex optimization medium (KSOM) for the culture of blastocysts, aiding in the study of early embryonic development.
Used in Investigative Research:
For chronic inhibition of GSK-3 to investigate its role in corticogenesis, 6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile is utilized to understand the impact of GSK-3 on brain development and related disorders.

Biological Activity

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.

Biochem/physiol Actions

CHIR99021 is a very potent inhibitor of Glycogen synthase kinase 3 (GSK3, IC50 values for GSK3α and GSK3β = 10 and 6.7 nM, respectively). There is no cross-reactivity against CDKs. CHIR99201 potentiates self-renewal of human and mouse embryonic stem cells, and enhances reprogramming of somatic cells into stem cells.

References

1) Bennett et al. (2002), Regulation of Wnt signaling during adipogenesis; J. Biol. Chem., 277 30998 2) Bennett et al. (2005), Regulation of osteoblastogenesis and bone mass by Wnt10b; Proc. Natl. Acad. Sci. USA, 102 3324 3) Mussmann et al. (2007), Inhibition of GSK3 promotes replication and survival of pancreatic beta cells; J. Biol. Chem., 282 12030 4) Manceur et al. (2011), Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors; Exp. Cell. Res., 317 2086 5) Takaoka et al. (2016), Live imaging of transforming growth factor-β activated kinase 1 activation in Lewis Lung carcinoma 3LL cells implanted into syngeneic mice and treated with polyinosinic:polycytidylic acid; Cancer Sci., 107 644 [Focus Citation]