AG1296 | PDGF Inhibitor | CAS#146535-11-7

MedKoo Cat#: 406209 | Name: AG1296

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Description:

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

AG1296 is a potent and specific inhibitor of the platelet-derived growth factor (PDGF) receptor tyrosine kinase.

Chemical Structure

AG1296

CAS#146535-11-7

Theoretical Analysis

MedKoo Cat#: 406209

Name: AG1296

CAS#: 146535-11-7

Chemical Formula: C16H14N2O2

Exact Mass: 266.1055

Molecular Weight: 266.29

Elemental Analysis: C, 72.16; H, 5.30; N, 10.52; O, 12.02

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,150.00	2 Weeks
1g	USD 2,950.00	2 Weeks
2g	USD 5,250.00	2 Weeks

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Related CAS #

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Synonym

AG1296; AG-1296; AG 1296; tyrphostin AG1296.

IUPAC/Chemical Name

2-Phenyl-6,7-dimethoxyquinoxaline ; 6,7-Dimethoxy-2-phenylquinoxaline

InChi Key

QNOXYUNHIGOWNY-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H14N2O2/c1-19-15-8-12-13(9-16(15)20-2)18-14(10-17-12)11-6-4-3-5-7-11/h3-10H,1-2H3

SMILES Code

COC1=C(OC)C=C2N=CC(C3=CC=CC=C3)=NC2=C1

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:

Tyrphostin AG1296 is an inhibitor of platelet-derived growth factor receptor (PDGFR), with an IC50 of 0.8 μM.

In vitro activity:

PDGFR-mediated signaling plays a crucial role in inhibiting apoptosis and increasing cell viability, so this study next examined tyrphostin AG1296-induced apoptosis in A375R cells. Figure 2A and B shows that the fraction of cells with a subG1 DNA content increased significantly after treatment with tyrphostin AG1296 (P<0.01). This study also observed the changes in nuclear morphology in A375R cells after treatment with tyrphostin AG1296. After treatment with tyrphostin AG1296, the nuclei of A375R cells showed a condensed and fragmented morphology, which is a characteristic of apoptosis (Figure 2C and D), suggesting that tyrphostin AG1296 could induce dramatic apoptosis in A375R cells. These data are consistent with the viability suppression results shown above. Reference: Onco Targets Ther. 2015; 8: 1043–1051. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437616/

In vivo activity:

All mice were given a high fat diet throughout the study. Atherosclerotic plaques were induced in carotid arteries by perivascular collar placement. The carotid plaques were successfully constructed in mice model as shown in Fig. 1A. In AG1296 group, plaque area decreased by 41.5% (p = 0.0041, Fig. 1B–C). This suggested that AG1296 inhibited atherosclerotic progression. Reference: Biochem Biophys Res Commun. 2017 Aug 5;489(4):426-431. https://pubmed.ncbi.nlm.nih.gov/28559142/

	Solvent	mg/mL	mM
Solubility
	DMSO	14.1	52.99
	DMF	5.0	18.78
	DMF:PBS (pH 7.2) (1:2)	0.3	1.13

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 266.29 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.

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. Contreras O, Córdova-Casanova A, Brandan E. PDGF-PDGFR network differentially regulates the fate, migration, proliferation, and cell cycle progression of myogenic cells. Cell Signal. 2021 Aug;84:110036. doi: 10.1016/j.cellsig.2021.110036. Epub 2021 May 8. PMID: 33971280. 2. Li Y, Li Y, Liu Q, Wang A. Tyrphostin AG1296, a platelet-derived growth factor receptor inhibitor, induces apoptosis, and reduces viability and migration of PLX4032-resistant melanoma cells. Onco Targets Ther. 2015 May 14;8:1043-51. doi: 10.2147/OTT.S70691. PMID: 25999739; PMCID: PMC4437616. 3. Gu M, Donato M, Guo M, Wary N, Miao Y, Mao S, Saito T, Otsuki S, Wang L, Harper RL, Sa S, Khatri P, Rabinovitch M. iPSC-endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension. Sci Transl Med. 2021 May 5;13(592):eaba6480. doi: 10.1126/scitranslmed.aba6480. PMID: 33952674. 4. Dong M, Zhou C, Ji L, Pan B, Zheng L. AG1296 enhances plaque stability via inhibiting inflammatory responses and decreasing MMP-2 and MMP-9 expression in ApoE-/- mice. Biochem Biophys Res Commun. 2017 Aug 5;489(4):426-431. doi: 10.1016/j.bbrc.2017.05.159. Epub 2017 May 27. PMID: 28559142.

In vitro protocol:

In vivo protocol:

1. Gu M, Donato M, Guo M, Wary N, Miao Y, Mao S, Saito T, Otsuki S, Wang L, Harper RL, Sa S, Khatri P, Rabinovitch M. iPSC-endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension. Sci Transl Med. 2021 May 5;13(592):eaba6480. doi: 10.1126/scitranslmed.aba6480. PMID: 33952674. 2. Dong M, Zhou C, Ji L, Pan B, Zheng L. AG1296 enhances plaque stability via inhibiting inflammatory responses and decreasing MMP-2 and MMP-9 expression in ApoE-/- mice. Biochem Biophys Res Commun. 2017 Aug 5;489(4):426-431. doi: 10.1016/j.bbrc.2017.05.159. Epub 2017 May 27. PMID: 28559142.

1: Gu M, Donato M, Guo M, Wary N, Miao Y, Mao S, Saito T, Otsuki S, Wang L, Harper RL, Sa S, Khatri P, Rabinovitch M. iPSC-endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension. Sci Transl Med. 2021 May 5;13(592):eaba6480. doi: 10.1126/scitranslmed.aba6480. PMID: 33952674; PMCID: PMC8762958. 2: Dong M, Zhou C, Ji L, Pan B, Zheng L. AG1296 enhances plaque stability via inhibiting inflammatory responses and decreasing MMP-2 and MMP-9 expression in ApoE-/- mice. Biochem Biophys Res Commun. 2017 Aug 5;489(4):426-431. doi: 10.1016/j.bbrc.2017.05.159. Epub 2017 May 27. PMID: 28559142. 3: Li Y, Li Y, Liu Q, Wang A. Tyrphostin AG1296, a platelet-derived growth factor receptor inhibitor, induces apoptosis, and reduces viability and migration of PLX4032-resistant melanoma cells. Onco Targets Ther. 2015 May 14;8:1043-51. doi: 10.2147/OTT.S70691. PMID: 25999739; PMCID: PMC4437616. 4: Lasota M, Bentke-Imiolek A, Skrzypek K, Bobrowska J, Jagusiak A, Bryniarska- Kubiak N, Zagajewski J, Kot M, Szydlak R, Lekka M, Laidler P, Majka M. Small- molecule inhibitor - tyrphostin AG1296 regulates proliferation, survival and migration of rhabdomyosarcoma cells. J Physiol Pharmacol. 2021 Dec;72(6). doi: 10.26402/jpp.2021.6.06. Epub 2022 Apr 2. PMID: 35377340. 5: Watanabe T, Ohtani T, Aihara M, Ishiuchi S. Enhanced antitumor effect of YM872 and AG1296 combination treatment on human glioblastoma xenograft models. J Neurosurg. 2013 Apr;118(4):838-45. doi: 10.3171/2012.11.JNS12362. Epub 2013 Jan 11. PMID: 23311938. 6: Lasota M, Klein A, Balwierz W. Cytostatic and cytotoxic effects of tyrphostin AG1296 on RMS cells. Contemp Oncol (Pozn). 2012;16(1):1-5. doi: 10.5114/wo.2012.27329. Epub 2012 Feb 29. PMID: 23788847; PMCID: PMC3687388. 7: Torres LA, Barbarroja N, Dorado G, Velasco F, López-Pedrera C. VEGF/KDR loop is a target of AG1296 in acute myeloid leukaemia showing FLT3-internal tandem duplications. Br J Haematol. 2009 Jun;145(6):836-8. doi: 10.1111/j.1365-2141.2009.07673.x. Epub 2009 Apr 8. PMID: 19388942. 8: Ueda S, Ikeda H, Mizuki M, Ishiko J, Matsumura I, Tanaka H, Shibayama H, Sugahara H, Takai E, Zhang X, Machii T, Kanakura Y. Constitutive activation of c-kit by the juxtamembrane but not the catalytic domain mutations is inhibited selectively by tyrosine kinase inhibitors STI571 and AG1296. Int J Hematol. 2002 Dec;76(5):427-35. doi: 10.1007/BF02982808. PMID: 12512837. 9: Kovalenko M, Rönnstrand L, Heldin CH, Loubtchenkov M, Gazit A, Levitzki A, Böhmer FD. Phosphorylation site-specific inhibition of platelet-derived growth factor beta-receptor autophosphorylation by the receptor blocking tyrphostin AG1296. Biochemistry. 1997 May 27;36(21):6260-9. doi: 10.1021/bi962553l. PMID: 9174341. 10: Tse KF, Novelli E, Civin CI, Bohmer FD, Small D. Inhibition of FLT3-mediated transformation by use of a tyrosine kinase inhibitor. Leukemia. 2001 Jul;15(7):1001-10. doi: 10.1038/sj.leu.2402199. PMID: 11455967. 11: Cheng SE, Lee IT, Lin CC, Hsiao LD, Yang CM. Thrombin induces ICAM-1 expression in human lung epithelial cells via c-Src/PDGFR/PI3K/Akt-dependent NF- κB/p300 activation. Clin Sci (Lond). 2014 Aug;127(3):171-83. doi: 10.1042/CS20130676. Erratum in: Clin Sci (Lond). 2020 Apr 30;134(8):1027-1030. PMID: 24506791. 12: Haraguchi S, Good RA, Day-Good NK. A potent immunosuppressive retroviral peptide: cytokine patterns and signaling pathways. Immunol Res. 2008;41(1):46-55. doi: 10.1007/s12026-007-0039-6. PMID: 18506644. 13: Lin CC, Lee IT, Chi PL, Hsieh HL, Cheng SE, Hsiao LD, Liu CJ, Yang CM. C-Src/Jak2/PDGFR/PKCδ-dependent MMP-9 induction is required for thrombin- stimulated rat brain astrocytes migration. Mol Neurobiol. 2014 Apr;49(2):658-72. doi: 10.1007/s12035-013-8547-y. Epub 2013 Sep 10. PMID: 24018979. 14: Schmidt-Arras D, Schwäble J, Böhmer FD, Serve H. Flt3 receptor tyrosine kinase as a drug target in leukemia. Curr Pharm Des. 2004;10(16):1867-83. doi: 10.2174/1381612043384394. PMID: 15180525. 15: Reiterer G, Yen A. Platelet-derived growth factor receptor regulates myeloid and monocytic differentiation of HL-60 cells. Cancer Res. 2007 Aug 15;67(16):7765-72. doi: 10.1158/0008-5472.CAN-07-0014. PMID: 17699781. 16: Kumar A, Salimath BP, Stark GB, Finkenzeller G. Platelet-derived growth factor receptor signaling is not involved in osteogenic differentiation of human mesenchymal stem cells. Tissue Eng Part A. 2010 Mar;16(3):983-93. doi: 10.1089/ten.TEA.2009.0230. PMID: 19839721. 17: Pei D, Liu N, Li D, Yan H, Wang QB, Fang Y, Xie L, Li HP. Inhibition of platelet-derived growth factor receptor β reduces reactive glia and scar formation after traumatic brain injury in mice. Brain Res Bull. 2017 Sep;134:121-127. doi: 10.1016/j.brainresbull.2017.06.020. Epub 2017 Jul 4. PMID: 28684344. 18: Tse KF, Allebach J, Levis M, Smith BD, Bohmer FD, Small D. Inhibition of the transforming activity of FLT3 internal tandem duplication mutants from AML patients by a tyrosine kinase inhibitor. Leukemia. 2002 Oct;16(10):2027-36. doi: 10.1038/sj.leu.2402674. PMID: 12357354. 19: Colanesi S, Taylor KL, Temperley ND, Lundegaard PR, Liu D, North TE, Ishizaki H, Kelsh RN, Patton EE. Small molecule screening identifies targetable zebrafish pigmentation pathways. Pigment Cell Melanoma Res. 2012 Mar;25(2):131-43. doi: 10.1111/j.1755-148X.2012.00977.x. PMID: 22252091. 20: Mony U, Jawad M, Seedhouse C, Russell N, Pallis M. Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment. Leukemia. 2008 Jul;22(7):1395-401. doi: 10.1038/leu.2008.125. Epub 2008 May 29. PMID: 18509353.