AG-490
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MedKoo CAT#: 200121

CAS#: 133550-30-8

Description: Tyrphostin AG490 is a JAK-2 specific inhibitor, which inhibits phosphorylation of EGFR and signal transducer and activator of transcription 3 [STAT-3], and subsequently reduce invasion and adhesion potential of malignant cells. The hematopoietic cancer c-Kit+, Jak-2+ and non hematopoietic tumors c-Kit+, HER-2+, JAK-2+ can be inhibited by the chemosensitizing agent AG490 causing programmed cell death.

Chemical Structure

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AG-490
CAS# 133550-30-8
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 200121
Name: AG-490
CAS#: 133550-30-8
Chemical Formula: C17H14N2O3
Exact Mass: 294.10
Molecular Weight: 294.300
Elemental Analysis: C, 69.38; H, 4.79; N, 9.52; O, 16.31

Price and Availability

Size Price Availability Quantity
50mg USD 450 2 Weeks
100mg USD 750 2 Weeks
200mg USD 1250 2 Weeks
500mg USD 2650 2 Weeks
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Synonym: AG 490; AG490; AG-490; Tyrphostin AG 490

IUPAC/Chemical Name: (E)-N-benzyl-2-cyano-3-(3,4-dihydroxyphenyl)acrylamide

InChi Key: TUCIOBMMDDOEMM-RIYZIHGNSA-N

InChi Code: 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+

SMILES Code: O=C(NCC1=CC=CC=C1)/C(C#N)=C/C2=CC=C(O)C(O)=C2

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: AG490 greatly inhibited osteoclast apoptosis. AG490 stimulated the phosphorylation of Akt and ERK. Adenovirus-mediated expression of dominant negative (DN)-Akt and DN-Ras in osteoclasts inhibited the survival of osteoclasts despite the presence of AG490. Cytochrome c release during osteoclast apoptosis was inhibited by AG490 treatment, but this effect was inhibited in the presence of LY294002 or U0126. AG490 suppressed the proapoptotic proteins Bad and Bim, which was inhibited in osteoclasts infected with DN-Akt and DN-Ras adenovirus. In addition, constitutively active MEK and myristoylated-Akt adenovirus suppressed the cleavage of pro-caspase-9 and -3 and inhibited osteoclast apoptosis induced by etoposide. Taken together, our results suggest that AG490 inhibited cytochrome c release into the cytosol at least partly by inhibiting the pro-apoptotic proteins Bad and Bim, which in turn suppressed caspase-9 and -3 activation, thereby inhibiting osteoclast apoptosis.      

Product Data:
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Biological target: AG490 (Tyrphostin AG490) is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.
In vitro activity: To explore the effect of blocking p-JAK2 on TNF-α-induced apoptosis in MC3T3-E1 cells, cells were pretreated with AG490 (0, 10, 20, and 40 μM), a specific JAK2 inhibitor, for 30 min before incubation with TNF-α (20 ng/ml, 48 h). Then, flow cytometry was performed after Annexin V and PI labeling. The results showed that AG490 significantly increased the percentage of apoptotic cells (Figs. 3A and B). Western blot analysis was used to detect p-JAK2, JAK2, and Cl-PARP expression. JAK2 phosphorylation decreased and reached the lowest point at 40 μM concentration. Meanwhile, the level of Cl-PARP increased (Figs. 3C–E). These results indicate that JAK2-blockage increases TNF-α-induced apoptosis in MC3T3-E1 cell. Reference: Pharmazie. 2020 Jun 1;75(6):255-260. https://pubmed.ncbi.nlm.nih.gov/32539921/
In vivo activity: Besides the effect of AG490 on neuroprotection against apoptosis, this study also observed the alternations of neurotrophins mediated by the inhibitor for neural repairment. The results from ELISA tests revealed that the i.p. injection of AG490 could increase the BNDF level from serum and brain tissue of MCAO mice (Figure 5a,b). Meanwhile, this study found the higher expression of BNDF (p < .05), neurotrophin‐3 (NT3), and also the neurotrophin receptor TrkB in the brain tissue (Figure 5c–e) in vivo. This evidence suggests that AG490 served as a pluripotent drug for neuroprotection in addition to its antiapoptotic activity. Reference: Brain Behav. 2021 Jan; 11(1): e01911. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821583/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 45.8 155.66
DMSO:PBS (pH 7.2) (1:10) 0.1 0.34
DMF 25.0 84.95
Ethanol 7.3 24.80

Preparing Stock Solutions

The following data is based on the product molecular weight 294.30 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ni Y, Zhang H, Zhang J, Li Z, Li Z. Inhibition of JAK2 by AG490 promotes TNF-α-induced apoptosis by inhibiting autophagy in MC3T3-E1 cells. Pharmazie. 2020 Jun 1;75(6):255-260. doi: 10.1691/ph.2020.0375. PMID: 32539921. 2. Zhou Y, Sun Y, Hou W, Ma L, Tao Y, Li D, Xu C, Bao J, Fan W. The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro. Int J Mol Med. 2020 Jul;46(1):191-200. doi: 10.3892/ijmm.2020.4592. Epub 2020 Apr 29. PMID: 32377718; PMCID: PMC7255460. 3. Fan L, Zhou L. AG490 protects cerebral ischemia/reperfusion injury via inhibiting the JAK2/3 signaling pathway. Brain Behav. 2021 Jan;11(1):e01911. doi: 10.1002/brb3.1911. Epub 2020 Oct 23. PMID: 33098244; PMCID: PMC7821583. 4. Tan G, Jiang L, Li G, Bai K. ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro. Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820948062. doi: 10.1177/1533033820948062. PMID: 33063634; PMCID: PMC7580129.
In vitro protocol: 1. Ni Y, Zhang H, Zhang J, Li Z, Li Z. Inhibition of JAK2 by AG490 promotes TNF-α-induced apoptosis by inhibiting autophagy in MC3T3-E1 cells. Pharmazie. 2020 Jun 1;75(6):255-260. doi: 10.1691/ph.2020.0375. PMID: 32539921. 2. Zhou Y, Sun Y, Hou W, Ma L, Tao Y, Li D, Xu C, Bao J, Fan W. The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro. Int J Mol Med. 2020 Jul;46(1):191-200. doi: 10.3892/ijmm.2020.4592. Epub 2020 Apr 29. PMID: 32377718; PMCID: PMC7255460.
In vivo protocol: 1. Fan L, Zhou L. AG490 protects cerebral ischemia/reperfusion injury via inhibiting the JAK2/3 signaling pathway. Brain Behav. 2021 Jan;11(1):e01911. doi: 10.1002/brb3.1911. Epub 2020 Oct 23. PMID: 33098244; PMCID: PMC7821583. 2. Tan G, Jiang L, Li G, Bai K. ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro. Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820948062. doi: 10.1177/1533033820948062. PMID: 33063634; PMCID: PMC7580129.

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1: Tan G, Jiang L, Li G, Bai K. ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro. Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820948062. doi: 10.1177/1533033820948062. PMID: 33063634; PMCID: PMC7580129.


2: Dimitrova P, Ivanovska N. Tyrphostin AG-490 inhibited the acute phase of zymosan-induced inflammation. Int Immunopharmacol. 2008 Nov;8(11):1567-77. doi: 10.1016/j.intimp.2008.06.013. Epub 2008 Jul 24. PMID: 18656556.


3: Sands JM, Blount MA. Novel activators of aquaporin 2 membrane expression for the treatment of nephrogenic diabetes insipidus: less is more. Focus on "High- throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration". Am J Physiol Cell Physiol. 2014 Oct 1;307(7):C595-6. doi: 10.1152/ajpcell.00184.2014. Epub 2014 Jun 18. PMID: 24944199; PMCID: PMC4187059.


4: Fan L, Zhou L. AG490 protects cerebral ischemia/reperfusion injury via inhibiting the JAK2/3 signaling pathway. Brain Behav. 2021 Jan;11(1):e01911. doi: 10.1002/brb3.1911. Epub 2020 Oct 23. PMID: 33098244; PMCID: PMC7821583.


5: Kirken RA, Erwin RA, Taub D, Murphy WJ, Behbod F, Wang L, Pericle F, Farrar WL. Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells. J Leukoc Biol. 1999 Jun;65(6):891-9. doi: 10.1002/jlb.65.6.891. PMID: 10380915.


6: Rashid S, Bibi N, Parveen Z, Shafique S. Inhibition of Janus kinases by tyrosine phosphorylation inhibitor, Tyrphostin AG-490. J Biomol Struct Dyn. 2015;33(11):2368-79. doi: 10.1080/07391102.2015.1050696. Epub 2015 Jun 23. PMID: 26017266.


7: Sareila O, Korhonen R, Kärpänniemi O, Nieminen R, Kankaanranta H, Moilanen E. JAK inhibitors AG-490 and WHI-P154 decrease IFN-gamma-induced iNOS expression and NO production in macrophages. Mediators Inflamm. 2006;2006(2):16161. doi: 10.1155/MI/2006/16161. PMID: 16883061; PMCID: PMC1592588.


8: Nomura N, Nunes P, Bouley R, Nair AV, Shaw S, Ueda E, Pathomthongtaweechai N, Lu HA, Brown D. High-throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration. Am J Physiol Cell Physiol. 2014 Oct 1;307(7):C597-605. doi: 10.1152/ajpcell.00154.2014. Epub 2014 Jun 18. PMID: 24944200; PMCID: PMC4187055.


9: Kumano K, Nakao A, Nakajima H, Miike S, Kurasawa K, Saito Y, Iwamoto I. Blockade of JAK2 by tyrphostin AG-490 inhibits antigen-induced eosinophil recruitment into the mouse airways. Biochem Biophys Res Commun. 2000 Apr 2;270(1):209-14. doi: 10.1006/bbrc.2000.2403. PMID: 10733929.


10: Wang LH, Kirken RA, Erwin RA, Yu CR, Farrar WL. 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. 1999 Apr 1;162(7):3897-904. PMID: 10201908.


11: Lanuti P, Bertagnolo V, Pierdomenico L, Bascelli A, Santavenere E, Alinari L, Capitani S, Miscia S, Marchisio M. Enhancement of TRAIL cytotoxicity by AG-490 in human ALL cells is characterized by downregulation of cIAP-1 and cIAP-2 through inhibition of Jak2/Stat3. Cell Res. 2009 Sep;19(9):1079-89. doi: 10.1038/cr.2009.80. Epub 2009 Jun 30. PMID: 19564891.


12: Zhang J, Ren B, Ni K, Liu Y, Ma Z. [Intrathecal injection of AG-490 reduces bone-cancer-induced spinal cord astrocyte reaction and thermal hyperalgesia in a mouse model]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Nov 28;43(11):1182-1187. Chinese. doi: 10.11817/j.issn.1672-7347.2018.11.003. PMID: 30643061.


13: Cirone M, Di Renzo L, Lotti LV, Conte V, Trivedi P, Santarelli R, Gonnella R, Frati L, Faggioni A. Primary effusion lymphoma cell death induced by bortezomib and AG 490 activates dendritic cells through CD91. PLoS One. 2012;7(3):e31732. doi: 10.1371/journal.pone.0031732. Epub 2012 Mar 7. PMID: 22412839; PMCID: PMC3296697.


14: Burdelya L, Catlett-Falcone R, Levitzki A, Cheng F, Mora LB, Sotomayor E, Coppola D, Sun J, Sebti S, Dalton WS, Jove R, Yu H. Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone. Mol Cancer Ther. 2002 Sep;1(11):893-9. PMID: 12481410.


15: Li DQ, Wan QL, Pathak JL, Li ZB. Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis. J Bone Miner Metab. 2017 Jul;35(4):355-365. doi: 10.1007/s00774-016-0773-8. Epub 2016 Sep 14. PMID: 27628046.


16: Jing N, Tweardy DJ. Targeting Stat3 in cancer therapy. Anticancer Drugs. 2005 Jul;16(6):601-7. doi: 10.1097/00001813-200507000-00002. PMID: 15930886.


17: Caceres-Cortes JR. A potent anti-carcinoma and anti-acute myeloblastic leukemia agent, AG490. Anticancer Agents Med Chem. 2008 Oct;8(7):717-22. doi: 10.2174/187152008785914752. PMID: 18855573.


18: Kahan BD. The potential role of rapamycin in pediatric transplantation as observed from adult studies. Pediatr Transplant. 1999 Aug;3(3):175-80. doi: 10.1034/j.1399-3046.1999.00036.x. PMID: 10487276.


19: Banes-Berceli AK, Ketsawatsomkron P, Ogbi S, Patel B, Pollock DM, Marrero MB. Angiotensin II and endothelin-1 augment the vascular complications of diabetes via JAK2 activation. Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1291-9. doi: 10.1152/ajpheart.00181.2007. Epub 2007 May 25. PMID: 17526654.


20: Banes-Berceli AK, Al-Azawi H, Proctor D, Qu H, Femminineo D, Hill-Pyror C, Webb RC, Brands MW. Angiotensin II utilizes Janus kinase 2 in hypertension, but not in the physiological control of blood pressure, during low-salt intake. Am J Physiol Regul Integr Comp Physiol. 2011 Oct;301(4):R1169-76. doi: 10.1152/ajpregu.00071.2011. Epub 2011 Aug 3. PMID: 21813872; PMCID: PMC3197339.