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 reactivity
5. AG 490 has also been used as a JAK2 inhibitor in human umbilical vein endothelial cells
6.
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.
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
