AG 490 Chemical Properties

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

Safety Information

Hazard Codes 

Xi,N,T

Risk Statements 

36/37/38-50-25

Safety Statements 

26-36-61-45

RIDADR 

UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI: all

WGK Germany 

1

RTECS 

UC6316197

HazardClass 

6.1

PackingGroup 

III

HS Code 

29269090

MSDS

• Language:English Provider:SigmaAldrich

AG 490 Usage And Synthesis

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.

Uses

Tyrphostin AG has been used to block IL-6 cytokine signaling to study its effects on glial cell reactivity⁵. AG 490 has also been used as a JAK2 inhibitor in human umbilical vein endothelial cells⁶.

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.

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 .

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

[1] L H WANG. JAK3, STAT, and MAPK signaling pathways as novel molecular targets for the tyrphostin AG-490 regulation of IL-2-mediated T cell response.[J]. Journal of immunology, 1999, 162 7: 3897-3904.
[2] NAFTALY MEYDAN. Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor[J]. Nature, 1996, 379 6566: 645-648. DOI:10.1038/379645a0
[3] VALERIYA GYURKOVSKA  Nina I. Tyrosine kinase inhibitor tyrphostin AG490 reduces liver injury in LPS-induced shock[J]. European journal of pharmacology, 2015, 751: Pages 118-126. DOI:10.1016/j.ejphar.2015.01.045
[4] LAN WU . ROS generated during early reperfusion contribute to intermittent hypobaric hypoxia-afforded cardioprotection against postischemia-induced Ca2 + overload and contractile dysfunction via the JAK2/STAT3 pathway[J]. Journal of molecular and cellular cardiology, 2015, 81: Pages 150-161. DOI:10.1016/j.yjmcc.2015.02.015

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