133550-30-8 Usage
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
Different sources of media describe the Uses of 133550-30-8 differently. You can refer to the following data:
1. 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.
2. 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.
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
Check Digit Verification of cas no
The CAS Registry Mumber 133550-30-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,3,5,5 and 0 respectively; the second part has 2 digits, 3 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 133550-30:
(8*1)+(7*3)+(6*3)+(5*5)+(4*5)+(3*0)+(2*3)+(1*0)=98
98 % 10 = 8
So 133550-30-8 is a valid CAS Registry Number.
133550-30-8Relevant articles and documents
COMPOUNDS FOR TREATMENT OF CELL PROLIFERATIVE DISEASES
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Page/Page column 22, (2008/06/13)
The present invention concerns compounds and their use to treat cell proliferative diseases such as cancer. Compounds of the present invention display significant potency as kinase inhibitors, cause the downregulation of c-myc, and inhibit the growth and survival of cancerous cell lines.
Structure-activity relationship of N-(phenylalkyl)cinnamides as novel NR2B subtype-selective NMDA receptor antagonists
Tamiz, Amir P.,Cai, Sui Xiong,Zhou, Zhang-Lin,Yuen, Po-Wai,Schelkun, Robert M.,Whittemore, Edward R.,Weber, Eckard,Woodward, Richard M.,Keana, John F. W.
, p. 3412 - 3420 (2007/10/03)
A novel series of N-(phenylalkyl)cinnamides related to N-(4- phenylbutyl)-3,4-dihydroxy-β-cyanocinnamide (6, an EGFR-K inhibitor with high antiproliferative activity) was synthesized and tested for antagonism at N-methyl-D-aspartate (NMDA) receptor subtypes. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The N- (phenylalkyl)cinnamides are selective antagonists of NR1(A)/2B receptors. Assayed under steady-state conditions, N-(4-phenylbutyl)-4-hydroxycinnamide (16) has an IC50 value of 77 nM and > 1000-fold selectivity with respect to NR1(A)/2A and NR1(A)/2C receptors. Potency at α1 adrenergic receptors is low for the four cinnamides tested. Inhibition of NR1(A)/2B receptors does not correlate with EGFR and ErbB2/neu tyrosine kinase inhibitor activity. The N-(phenylalkyl)cinnamide series we describe provides a novel and structurally diverse framework for designing new NR2B-selective NMDA antagonists as potential CNS therapeutics.
