DC Chemicals Limited
China
Product Name: AG490
Price: $200.0/100mg $400.0/250mg $800.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

Dayang Chem (Hangzhou) Co., Ltd.
China
Product Name: N-BENZYL-3,4-DIHYDROXY-BENZYLIDENECYANOACETAMIDE (AG-490)
Price: $Inquiry/100g $Inquiry/1kg $Inquiry/100kg $Inquiry/1000kg
Purity: 98.0%
Stocking Period: Inquiry
Contact: Ms Wang

Zhejiang Hangyu API Co., Ltd
China
Product Name: TIANFU-CHEM AG 490
Price: ￥Inquiry/1kg
Purity: 99.5%
Stocking Period: Inquiry
Contact: Vinnie

133550-30-8

133550-30-8 structure

133550-30-8 structure

Name: Tyrphostin B42 (AG-490)
Chemical Name: Tyrphostin AG 490
CAS Number: 133550-30-8
Molecular Formula: C₁₇H₁₄N₂O₃
Molecular Weight: 294.305
Catalog: Biochemical Amino acids and their derivatives Tyrosine derivatives
Create Date: 2018-02-17 08:00:00
Modify Date: 2024-01-08 20:48:30
AG-490 is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.

Name	Tyrphostin AG 490
Synonyms	N-Benzyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylamide (E)-N-benzyl-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enamide (E)-N-Benzyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylamide Tyrphostin B42 (2E)-N-Benzyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylamide MFCD00209833 2-Propenamide, 2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-, (2E)- AG490 AG-490

Description	AG-490 is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.
Related Catalog	Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> JAK/STAT Signaling >> EGFR Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR Signaling Pathways >> JAK/STAT Signaling >> STAT Signaling Pathways >> Stem Cell/Wnt >> STAT Research Areas >> Cancer
Target	EGFR Stat-3
In Vitro	AG490 inhibits the activation of Stat-3 by selectively blocking JAK2. AG490 is used to selectively inhibit JAK/Stat-3 activation. At a dose of 10 μM, Stat-3 phosphorylation is decreased by >95% and cell viability is maintained. AG490 at a dose of 10 μM results in >95% decrease in pStat-3 in EGF-stimulated A431 cells with no effect on Stat-3 mass[1]. AG-490 is a potent inhibitor of the JAK3/STAT, JAK3/AP-1, and JAK3/MAPK pathways and their cellular consequences. AG-490 abolishes IL-2-inducible [3H]thymidine incorporation in a dose-dependent manner, displaying an IC50 of 25 μM. AG-490 potently inhibits IL-2-mediated proliferation in T cells, results distinct from previous studies that showed this agent induced apoptosis in ALL cells while exerting apparently no effects on the growth of mitogen-stimulated normal T cells[2].
In Vivo	AG490 significantly inhibits the development of type 1 diabetes (T1D) (p = 0.02, p = 0.005; at two different time points). Monotherapy of newly diagnosed diabetic NOD mice with AG490 (1 mg/mouse) markedly results in disease remission in treated animals (n=23) in comparision to the absolute inability (0%; 0/10, p=0.003, Log-rank test) of DMSO and sustained eugluycemia is maintained for several months following drug withdrawal[3]. AG490 (1-10 µg) significantly attenuates ʎ-carrageenan-induced thermal hyperalgesia in a dose-dependent manner. AG490 also reduces mechanical hyperalgesia[4].
Cell Assay	A colorimetric cell proliferation assay is performed using the CellTiter 96 kit. Briefly, A431 cells are plated in 96-well plates (2000 cells/well) and cultured in DMEM/HAM's F-12 supplemented with 10% FCS for 24 h. Cells are incubated in serum-free media for 24 h. EGF (10 ng/mL) is added to all wells. Tyrphostin AG1478 (0.25 mM) and AG490 (10 mM) are added alone or in combination and the culture is incubated for the appropriate time. Medium is aspirated and CellTiter 96 Aqueous One Solution Reagent (20 μL) is added to each well. The plates are incubated at 37°C for up to 1 h and absorbance recorded at 490 nm using a 96-well plate reader. Data are derived from at least three independent experiments (in triplicate) for the both single agents and combination studies. IC50 values for Tyrphostin AG1478 (EGFR inhibitor) and AG490 (JAK/STAT inhibitor) are determined. The growth inhibitory effects of the combination are quantified using the Calucsyn software program[1].
Animal Admin	Mice[3] Female NOD/LtJ, NOD.Scid, and BALB/c mice are used. One vial of compound containing 5 mg of AG490 is injected into5 mice (1 mg/mouse) via the i.p route. The control groups are receive the same volume of the vehicle under the same regimens and conditions. Rats[4] A total of 28 Male Sprague-Dawley rats (250-300 g) are used. The experiments are performed in rats 48 h after ʎ-carrageenan injection. A total of 4 groups (n=6) of rats are randomly included in the dose-response study. Group 1 is the vehicle control, which receive 100 µL i.pl. injection of 3.5% DMSO in saline. Groups 2-4 are injected with 3 different doses of AG490 (1, 5 or 10 µg). To study the effects of naloxone on AG490-induced antinociception, an additional group of rats (group 5; n=4) is observed. Group 5 is co-administered with AG490 (10 µg) and Naloxone (10 µg). The drugs are administered i.pl. in a volume of 100 µl. As reported earlier, the in vivo pharmacological effects of AG490 are observed 4 h after treatment. Thus, the behavioral tests are performed before (baseline assessment) and 4 h after treatment. First, the rats are subjected to the thermal hyperalgesia test; 10 min later, the paw pressure test is performed on the same set of rats. All the experiments are performed between 8:00 a.m. and 2:00 p.m. to reduce the confounding influence of diurnal variations, and all the procedures are performed in a blinded fashion.
References	[1]. Dowlati A, et al. Combined inhibition of epidermal growth factor receptor and JAK/STAT pathways results in greater growth inhibition in vitro than single agent therapy. Mol Cancer Ther. 2004 Apr;3(4):459-63 [2]. Wang LH, et al. JAK3, STAT, and MAPK signaling pathways as novel molecular targets for the tyrphostin AG-490 regulation ofIL-2-mediated T cell response. J Immunol. 1999 Apr 1;162(7):3897-904. [3]. Davoodi-Semiromi A, et al. The tyrphostin agent AG490 prevents and reverses type 1 diabetes in NOD mice. PLoS One. 2012;7(5):e36079. [4]. Cheppudira BP, et al. Anti-hyperalgesic effects of AG490, a Janus kinase inhibitor, in a rat model of inflammatory pain. Biomed Rep. 2015 Sep;3(5):703-706.

Density	1.3±0.1 g/cm3
Boiling Point	615.2±55.0 °C at 760 mmHg
Melting Point	215°C(lit.)
Molecular Formula	C₁₇H₁₄N₂O₃
Molecular Weight	294.305
Flash Point	325.9±31.5 °C
Exact Mass	294.100433
PSA	93.35000
LogP	2.11
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.679
Storage condition	−20°C
Water Solubility	ethanol: 5 mg/mL

Symbol	GHS06, GHS09
Signal Word	Danger
Hazard Statements	H301-H400
Precautionary Statements	P273-P301 + P310
Hazard Codes	Xi: Irritant;
Risk Phrases	R36/37/38
Safety Phrases	26-36
RIDADR	UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI: all
WGK Germany	1
RTECS	UC6316197
Packaging Group	III
HS Code	2926909090

10412-93-8 structure

10412-93-8

139-85-5 structure

139-85-5

~81%

133550-30-8 structure

133550-30-8

Literature: Gazit, Aviv; Osherov, Nir; Posner, Israel; Yaish, Pnina; Poradosu, Enrique; et al. Journal of Medicinal Chemistry, 1991 , vol. 34, # 6 p. 1896 - 1907

100-46-9 structure

100-46-9

~%

133550-30-8 structure

133550-30-8

Literature: Journal of Medicinal Chemistry, , vol. 42, # 17 p. 3412 - 3420

Precursor 3
10412-93-8 139-85-5 100-46-9
DownStream 0

HS Code	2926909090
Summary	HS:2926909090 other nitrile-function compounds VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:30.0%