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MedKoo Cat#: 401019 | Name: AG-1478
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Protein tyrosine kinase (PTK) inhibitors are potential antiproliferative agents for diseases caused by the hyperactivity of PTK. Tyrphostins are a class of antiproliferative compounds which act as PTK blockers. PTK inhibitors which preferentially inhibit the epidermal growth factor receptor (EGFR) kinase and block EGFR-dependent cell proliferation. AG-1478 is an inhibitor of EGFR kinase with an IC50 value of 3 nM.1 Due to its potency and selectivity, AG-1478 has been used in a broad range of studies. It reversibly inhibits rat brain Kv1.5 potassium channels (IC50 = 9.8 µM) independent of protein tyrosine kinase (PTK) activity.2 AG-1478 also inhibits the growth of leiomyoma and myometrium cell cultures with IC50 values of 5.6 and 5.7 µM, respectively. This inhibitor suppresses MAP kinase activation and strongly inhibits induction of fos gene expression and DNA synthesis.

Chemical Structure

AG-1478
CAS#153436-53-4 (free base)

Theoretical Analysis

MedKoo Cat#: 401019

Name: AG-1478

CAS#: 153436-53-4 (free base)

Chemical Formula: C16H14ClN3O2

Exact Mass: 315.0775

Molecular Weight: 315.75

Elemental Analysis: C, 60.86; H, 4.47; Cl, 11.23; N, 13.31; O, 10.13

Price and Availability

Size Price Availability Quantity
100mg USD 450.00 2 Weeks
200mg USD 750.00 2 Weeks
500mg USD 1,550.00 2 Weeks
1g USD 2,650.00 2 Weeks
2g USD 4,650.00 2 Weeks
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Related CAS #
153436-53-4 (free base) 170449-18-0 (HCl)
Synonym
AG1478; AG-1478; AG 1478; Tyrphostin AG 1478.
IUPAC/Chemical Name
N-(3-chlorophenyl)-6,7-dimethoxyquinazolin-4-amine
InChi Key
GFNNBHLJANVSQV-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H14ClN3O2/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11/h3-9H,1-2H3,(H,18,19,20)
SMILES Code
COC1=CC2=NC=NC(NC3=CC=CC(Cl)=C3)=C2C=C1OC
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
       
Product Data
Product Data
Instruction
View handling instruction
Biological target:
AG-1478 (Tyrphostin AG-1478) is a selective EGFR tyrosine kinase inhibitor with IC50 of 3 nM. AG-1478 has antiviral effects against HCV and encephalomyocarditis virus (EMCV).
In vitro activity:
To this end, HeLa cells were infected with either EMCV or CVB3 for 30 min, after which virus-containing medium was replaced with compound-containing medium. Eight hours later, cells were lysed by freeze-thawing to determine the total virus titers by endpoint dilution. As we have previously shown, AG1478 did not perturb CVB3 replication (Fig. 1B). However, EMCV was inhibited by AG1478 in a dose-dependent manner, with a complete inhibition at 25 μM. The inhibition observed with AG1478 was comparable to that obtained with 10 μM AL-9 (Fig. 1B). In parallel, a cell viability assay was performed to verify that the antiviral activity of AG1478 was not due to cytotoxic effects (Fig. 1B). Reference: Antimicrob Agents Chemother. 2016 Oct; 60(10): 6402–6406. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038282/
In vivo activity:
As expected, CD31 was markedly increased in retinas of DM mice compared with the non-diabetic group (Figure 5A). In addition, the number of retinal vessels was significantly increased in the DM group (Figure 5C). However, treatment with AG1478 markedly reduced the number of CD31-positive cells and vessel density in retinas of DM mice (Figure 5A,C, respectively), supporting an anti-angiogenic effect of AG1478. Reference: Clin Exp Pharmacol Physiol. 2019 Jan;46(1):75-85. https://pubmed.ncbi.nlm.nih.gov/30221384/
Solvent mg/mL mM comments
Solubility
DMSO 42.2 133.55
DMSO:PBS (pH 7.2) (1:8) 0.1 0.32
DMF 1.0 3.17
Ethanol 0.5 1.58
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 315.75 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. Dorobantu CM, Harak C, Klein R, van der Linden L, Strating JR, van der Schaar HM, Lohmann V, van Kuppeveld FJ. Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6402-6. doi: 10.1128/AAC.01331-16. PMID: 27480860; PMCID: PMC5038282. 2. Ma L, Yan H, Zhou Q. AG1478 inhibits the migration and invasion of cisplatin-resistant human lung adenocarcinoma cells via the cell cycle regulation by matrix metalloproteinase-9. Oncol Lett. 2014 Aug;8(2):921-927. doi: 10.3892/ol.2014.2224. Epub 2014 Jun 4. PMID: 25009665; PMCID: PMC4081427. 3. Ju X, Yang X, Yan T, Chen H, Song Z, Zhang Z, Wu W, Wang Y. EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy. Clin Exp Pharmacol Physiol. 2019 Jan;46(1):75-85. doi: 10.1111/1440-1681.13029. Epub 2018 Sep 16. PMID: 30221384. 4. Shimizu S, Takezawa-Yasuoka K, Ogawa T, Tojima I, Kouzaki H, Shimizu T. The epidermal growth factor receptor inhibitor AG1478 inhibits eosinophilic inflammation in upper airways. Clin Immunol. 2018 Mar;188:1-6. doi: 10.1016/j.clim.2017.11.010. Epub 2017 Nov 26. PMID: 29183867.
In vitro protocol:
1. Dorobantu CM, Harak C, Klein R, van der Linden L, Strating JR, van der Schaar HM, Lohmann V, van Kuppeveld FJ. Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6402-6. doi: 10.1128/AAC.01331-16. PMID: 27480860; PMCID: PMC5038282. 2. Ma L, Yan H, Zhou Q. AG1478 inhibits the migration and invasion of cisplatin-resistant human lung adenocarcinoma cells via the cell cycle regulation by matrix metalloproteinase-9. Oncol Lett. 2014 Aug;8(2):921-927. doi: 10.3892/ol.2014.2224. Epub 2014 Jun 4. PMID: 25009665; PMCID: PMC4081427.
In vivo protocol:
1. Ju X, Yang X, Yan T, Chen H, Song Z, Zhang Z, Wu W, Wang Y. EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy. Clin Exp Pharmacol Physiol. 2019 Jan;46(1):75-85. doi: 10.1111/1440-1681.13029. Epub 2018 Sep 16. PMID: 30221384. 2. Shimizu S, Takezawa-Yasuoka K, Ogawa T, Tojima I, Kouzaki H, Shimizu T. The epidermal growth factor receptor inhibitor AG1478 inhibits eosinophilic inflammation in upper airways. Clin Immunol. 2018 Mar;188:1-6. doi: 10.1016/j.clim.2017.11.010. Epub 2017 Nov 26. PMID: 29183867.
1: Han Y, Caday CG, Nanda A, Cavenee WK, Huang HJ. Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing truncated rather than wild-type epidermal growth factor receptors. Cancer Res. 1996 Sep 1;56(17):3859-61. PMID: 8752145. 2: Khattab M, Wang F, Clayton AH. UV-Vis spectroscopy and solvatochromism of the tyrosine kinase inhibitor AG-1478. Spectrochim Acta A Mol Biomol Spectrosc. 2016 Jul 5;164:128-32. doi: 10.1016/j.saa.2016.04.009. Epub 2016 Apr 12. PMID: 27092736. 3: Choi BH, Choi JS, Rhie DJ, Yoon SH, Min DS, Jo YH, Kim MS, Hahn SJ. Direct inhibition of the cloned Kv1.5 channel by AG-1478, a tyrosine kinase inhibitor. Am J Physiol Cell Physiol. 2002 Jun;282(6):C1461-8. doi: 10.1152/ajpcell.00398.2001. PMID: 11997261. 4: Weglicki WB, Kramer JH, Spurney CF, Chmielinska JJ, Mak IT. The EGFR tyrosine kinase inhibitor tyrphostin AG-1478 causes hypomagnesemia and cardiac dysfunction. Can J Physiol Pharmacol. 2012 Aug;90(8):1145-9. doi: 10.1139/y2012-023. Epub 2012 May 30. PMID: 22646904; PMCID: PMC3734545. 5: Stekelenburg J, Klein BY, Ben-Bassat H, Rojansky N. Opposing effects of cyclosporin A and tyrphostin AG-1478 indicate a role for Src protein in the cellular control of mineralization. J Cell Biochem. 1998 Oct 1;71(1):116-26. doi: 10.1002/(sici)1097-4644(19981001)71:1<116::aid-jcb12>3.0.co;2-l. PMID: 9736460. 6: Clayton AH, Perugini MA, Weinstock J, Rothacker J, Watson KG, Burgess AW, Nice EC. Fluorescence and analytical ultracentrifugation analyses of the interaction of the tyrosine kinase inhibitor, tyrphostin AG 1478-mesylate, with albumin. Anal Biochem. 2005 Jul 15;342(2):292-9. doi: 10.1016/j.ab.2005.04.002. PMID: 15913535. 7: Hegab AE, Sakamoto T, Nomura A, Ishii Y, Morishima Y, Iizuka T, Kiwamoto T, Matsuno Y, Homma S, Sekizawa K. Niflumic acid and AG-1478 reduce cigarette smoke-induced mucin synthesis: the role of hCLCA1. Chest. 2007 Apr;131(4):1149-56. doi: 10.1378/chest.06-2031. PMID: 17426222. 8: Osherov N, Levitzki A. Tyrphostin AG 494 blocks Cdk2 activation. FEBS Lett. 1997 Jun 30;410(2-3):187-90. doi: 10.1016/s0014-5793(97)00580-2. PMID: 9237626. 9: Klein BY, Tepper SH, Gal I, Shlomai Z, Ben-Bassat H. Opposing effects of tyrosine kinase inhibitors on mineralization of normal and tumor bone cells. J Cell Biochem. 1997 Jun 1;65(3):420-9. PMID: 9138097. 10: Li F, Zhou Y, Cheng N, Mao H, Jiang L, Li N, Li Q, de Jong MC, Pawlik TM. Epidermal growth factor receptor as a target for anti-proliferative treatment of proliferative cholangitis in hepatolithiasis. J Surg Res. 2011 Mar;166(1):87-94. doi: 10.1016/j.jss.2009.09.058. Epub 2009 Nov 11. PMID: 20097367. 11: Miyakawa M, Konno T, Kohno T, Kikuchi S, Tanaka H, Kojima T. Increase in Epithelial Permeability and Cell Metabolism by High Mobility Group Box 1, Inflammatory Cytokines and TPEN in Caco-2 Cells as a Novel Model of Inflammatory Bowel Disease. Int J Mol Sci. 2020 Nov 10;21(22):8434. doi: 10.3390/ijms21228434. PMID: 33182652; PMCID: PMC7696423. 12: Yu JL, Xing R, Milsom C, Rak J. Modulation of the oncogene-dependent tissue factor expression by kinase suppressor of ras 1. Thromb Res. 2010 Jul;126(1):e6-10. doi: 10.1016/j.thromres.2010.04.014. PMID: 20553947. 13: You M, Xia X, Li H, Wu J, Rong R, Zeng Z, Xiong K, Huang J, Tang L, Lei H, Wu W, Ji D. Normal vitreous promotes angiogenesi via the epidermal growth factor receptor. FASEB J. 2020 Nov;34(11):14799-14809. doi: 10.1096/fj.201902862RRR. Epub 2020 Sep 10. PMID: 32910506. 14: Nagane M, Lin H, Cavenee WK, Huang HJ. Aberrant receptor signaling in human malignant gliomas: mechanisms and therapeutic implications. Cancer Lett. 2001 Jan;162 Suppl:S17-S21. doi: 10.1016/s0304-3835(00)00648-0. PMID: 11164186. 15: Beaulieu Leclerc V, Roy O, Santerre K, Proulx S. TGF-β1 promotes cell barrier function upon maturation of corneal endothelial cells. Sci Rep. 2018 Mar 13;8(1):4438. doi: 10.1038/s41598-018-22821-9. PMID: 29535350; PMCID: PMC5849742. 16: Zhou X, Zhu L, Bondy C, Wang J, Luo Q, Chen Y. AG1478 Elicits a Novel Anti- Influenza Function via an EGFR-Independent, GBF1-Dependent Pathway. Int J Mol Sci. 2022 May 16;23(10):5557. doi: 10.3390/ijms23105557. PMID: 35628375; PMCID: PMC9145774. 17: Koumbadinga GA, Petitclerc E, Bouthillier J, Adam A, Marceau F. Receptor tyrosine kinases as mediators of injury-induced bradykinin B1 receptor expression in rabbit aortic smooth muscle. Eur J Pharmacol. 2009 Mar 15;606(1-3):233-9. doi: 10.1016/j.ejphar.2008.12.058. Epub 2009 Jan 21. PMID: 19374866. 18: Götte M, Sofeu Feugaing DD, Kresse H. Biglycan is internalized via a chlorpromazine-sensitive route. Cell Mol Biol Lett. 2004;9(3):475-81. PMID: 15332124. 19: Gerlach JP, van Buggenum JAG, Tanis SEJ, Hogeweg M, Heuts BMH, Muraro MJ, Elze L, Rivello F, Rakszewska A, van Oudenaarden A, Huck WTS, Stunnenberg HG, Mulder KW. Combined quantification of intracellular (phospho-)proteins and transcriptomics from fixed single cells. Sci Rep. 2019 Feb 6;9(1):1469. doi: 10.1038/s41598-018-37977-7. PMID: 30728416; PMCID: PMC6365588. 20: Feng PH, Hsiung TC, Kuo HP, Huang CD. Cross-talk between bradykinin and epidermal growth factor in regulating IL-6 production in human airway smooth muscle cells. Chang Gung Med J. 2010 Jan-Feb;33(1):92-9. PMID: 20184800.