| Identification | Back Directory | [Name]
AG 490 | [CAS]
133550-30-8 | [Synonyms]
AG 490
Zinc02557947
TYRPHOSTIN B42
TYROPHOSTIN AG490
TYRPHOSTIN AG 490
bis-tyrphostin B42
AG-490 (Tyrphostin B42)
AG 490 (Tyrphostin AG 490)
Tyrphostin AG 490
AG 490
AG 490(Tyrphostin AG 490,Tyrphostin B42)
A-CYANO-(3,4-DIHYDROXY)-N-BENZYLCINNAMIDE
N-BENZYL-3,4-DIHYDROXY-ALPHA-CYANOCINNAMIDE
A-CYANO-(3,4-DIHYDROXY)-N-BENZYLCINNAMAMIDE
ALPHA-CYANO-(3,4-DIHYDROXY)-N-BENZYLCINNAMIDE
N-BENZYL-3,4-DIHYDROXY-BENZYLIDENECYANOACETAMIDE
N-Benzyl-2-cyano-3-(3,4-dihydroxy-phenyl)-acrylamide
(E)-N-benzyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylamide
2-cyano-3-(3,4-dihydroxyphenyl)-n-(benzyl)-2-propenamide
2-CYANO-3-[3,4-DIHYDROXYPHENYL]-N-[PHENYLMETHYL]-2-PROPENAMIDE
(E)-2-CYANO-3-(3,4-DIHYDROPHENYL)-N-(PHENYLMETHYL)-2-PROPENAMIDE
(2E)-2-Cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide
2-PropenaMide, 2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylMethyl)-, (2E)-
(2E)-2-Cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide AG-490(Tyrphostin B42) | [Molecular Formula]
C17H14N2O3 | [MDL Number]
MFCD00209833 | [MOL File]
133550-30-8.mol | [Molecular Weight]
294.3 |
| Chemical Properties | Back Directory | [Melting point ]
215°C(lit.) | [Boiling point ]
615.2±55.0 °C(Predicted) | [density ]
1.337 | [storage temp. ]
−20°C
| [solubility ]
ethanol: 5 mg/mL
| [form ]
solid
| [pka]
8.75±0.10(Predicted) | [color ]
yellow
| [biological source]
synthetic (organic) | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO, DMF, or ethanol may be stored at -20°C for up to 1 month. | [InChI]
InChI=1S/C17H14N2O3/c18-10-14(8-13-6-7-15(20)16(21)9-13)17(22)19-11-12-4-2-1-3-5-12/h1-9,20-21H,11H2,(H,19,22)/b14-8+ | [InChIKey]
TUCIOBMMDDOEMM-ZSOIEALJSA-N | [SMILES]
C(NCC1=CC=CC=C1)(=O)/C(/C#N)=C/C1=CC=C(O)C(O)=C1 |
| Hazard Information | Back Directory | [Usage]
AG 490 is a potent epidermal growth factor receptor kinase autophosphorylation inhibitor with an IC50 of 100 nM and 56.8 μM for EGFR and JAK, respectively. | [Biological Activity]
Selective inhibitor of EGF receptor tyrosine kinase (IC 50 values are 2 and 13.5 μ M for EGFR and ErbB2 respectively). Inhibitor of JAK2, JAK3/STAT, JAK3/AP-1 and JAK3/MAPK pathways and potently inhibits cytokine-independent cell growth in vitro and tumor cell invasion in vivo . | [Description]
AG-490 (133550-30-8) is a potent inhibitor of the JAK2 tyrosine kinase. In acute lymphoblastic leukemia (ALL) cells, which abundantly express JAK-2, AG-490 dose-dependently blocked cell growth, induced apoptosis and inhibited DNA synthesis. Blocks the growth of all pre-B ALL cells with no effect on normal B or T cells. Does not significantly inhibit other kinases such as Lck, Lyn, Btk, Syk and Src. Reduces liver injury in LPS-induced shock.3 AG-490 is a useful tool for exploring the role of JAK2/STAT3 pathway in physiologic processes.4 | [Uses]
AG 490 is a potent epidermal growth factor receptor kinase autophosphorylation inhibitor with an IC50 of 100 nM and 56.8 μM for EGFR and JAK, respectively. | [Definition]
ChEBI: Tyrphostin B42 is a monocarboxylic acid amide obtained by formal condensation of the carboxy group of (2E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoic acid with the amino group of benzylamine. It has a role as an EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, an antioxidant, a STAT3 inhibitor, an anti-inflammatory agent, an apoptosis inducer and a geroprotector. It is an enamide, a monocarboxylic acid amide, a nitrile, a member of catechols and a secondary carboxamide. | [Biochem/physiol Actions]
Jak-2 protein tyrosine kinase (PTK) inhibitor. Inhibits interleukin 2 (IL-2) driven mitogenesis and triggers apoptosis of tumor cells in Sezary syndrome, a leukemic variant of cutaneous T cell lymphoma. | [Synthesis]
Example 1; General method of compound synthesis; (E)-N-benzyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylamide was prepared by the following general procedure. Benzylamine (3.0 g, 28 mmol) and ethyl cyanoacetate (4.7 g, 42 mmol) were dissolved in acetonitrile (20 mL), stirred and refluxed for 4 hours. The benzylamine in this general method can be replaced by other R3 substituents. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure to give an oil, which solidified to the intermediate N-benzyl-2-cyanoacetamide upon standing. An off-white powder of 3.28 g (68% yield) was obtained by ethyl acetate precipitation. Subsequently, N-benzyl-2-cyanoacetamide (1.3 g, 7.5 mmol), 3,4-dihydroxybenzaldehyde (1.1 g, 8.2 mmol) and a catalytic amount of piperidine (5 drops) were mixed and stirred under reflux conditions for 3 hours. The reaction mixture was purified by fast column chromatography (ethyl acetate as eluent) and then recrystallized twice by water/ethanol solvent mixture to give 0.8 g (36% yield) of the target product in white powder form. | [storage]
Room temperature | [References]
References/Citations
1) Wang et al. (1999), JAK3, STAT, and MAPK signaling pathways as novel molecular targets for the tyrphostin AG-490 regulation of IL-2-mediated T cell response; J. Immunol. 162 3897
2) Meydan et al. (1996), Inhibition of acute lymphoblastic leukaemia by Jak-2 inhibitor; Nature, 379 645
3) Gyurkovska and Ivanovaska (2015), Tyrosine kinase inhibitor tyrphostin AG490 reduces liver injury in LPS-induced shock; Eur. J. Pharmacol., 751 118
4) Wu et al. (2015), ROS generated during early reperfusion contribute to intermittent hypobaric hypoxia-afforded cardioprotection against postischemia-induced Ca(+2) overload and contractile dysfunction via the JAK2/STAT3 pathway; J. Mol. Cell. Cardiol., 81 150 |
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