133550-30-8 Usage
Description
AG 490, also known as Tyrphostin AG, is a potent inhibitor of the JAK2 tyrosine kinase with an IC50 of 100 nM for EGFR and 56.8 μM for JAK. It selectively targets JAK2, blocking its autophosphorylation and inhibiting cell growth, inducing apoptosis, and suppressing DNA synthesis in acute lymphoblastic leukemia (ALL) cells. AG 490 does not significantly inhibit other kinases such as Lck, Lyn, Btk, Syk, and Src, making it a useful tool for studying the role of the JAK2/STAT3 pathway in various physiological processes.
Uses
Used in Cancer Research:
AG 490 is used as a JAK2 inhibitor for studying the role of the JAK2/STAT3 pathway in cancer development and progression. It has been shown to block cell growth and induce apoptosis in ALL cells, making it a valuable tool for investigating the therapeutic potential of JAK2 inhibition in cancer treatment.
Used in Immunology Research:
AG 490 is used as an IL-6 cytokine signaling blocker to study its effects on glial cell reactivity. This application helps researchers understand the role of IL-6 signaling in immune responses and the potential of AG 490 as a modulator of immune cell function.
Used in Endothelial Cell Research:
AG 490 is used as a JAK2 inhibitor in human umbilical vein endothelial cells to study the role of JAK2 in endothelial cell function and its potential as a therapeutic target for various vascular-related diseases.
Used in Shock and Inflammation Research:
AG 490 has been shown to reduce liver injury in LPS-induced shock, making it a useful tool for studying the role of JAK2 in inflammatory responses and the potential of AG 490 as an anti-inflammatory agent.
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.
