Tyrphostin AG1296 is a potent and selective inhibitor of platelet-derived growth factor receptor (PDGFR), with an IC50 of 0.8 μM. Tyrphostin AG1296 inhibits signaling of human PDGF α- and β-receptors as well as of the related stem cell factor receptor (c-Kit). Tyrphostin AG1296 is also a potent inhibitor of FLT3, with an IC50 in the micromolar range[1][2][3].
IC50 & Target
PDGFRα
PDGFRβ
体外研究 (In Vitro)
Tyrphostin AG1296 (0.625-20 μM; 72 h) suppresses viability of PLX4032-resistant melanoma cells[4]. Tyrphostin AG1296 (2.5-20 μM; 48 h) induces apoptosis of A375R cells[4]. Tyrphostin AG1296 (5 and 20 μM; 2 h) inhibits PDGFR phosphorylation in A375R cells[4]. Tyrphostin AG1296 (0.0625-1 μM; 8 h) inhibits migration of A375R cells[4].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[4]
Cell Line:
PLX4032-resistant cell lines (A375R and SK-MEL-5R)
Concentration:
0.625, 1.25, 5, 20 μM
Incubation Time:
72 h
Result:
Reduced the viability of both PLX4032-sensitive and PLX4032-resistant cell lines.
Apoptosis Analysis[4]
Cell Line:
A375R cells
Concentration:
2.5, 5, 10, 20 μM
Incubation Time:
48 h
Result:
Induced dramatic apoptosis in A375R cells.
Western Blot Analysis[4]
Cell Line:
A375R cells
Concentration:
5, 20 μM
Incubation Time:
2 h
Result:
Inhibited phosphorylation of both PDGFR-α and PDGFR-β.
体内研究 (In Vivo)
Tyrphostin AG1296 (40 and 80 mg/kg; i.p. daily for two weeks) suppresses A375R tumor growth in vivo[4]. Tyrphostin AG1296 (2 mg/kg; i.p. every other day for 3 weeks) inhibits the atherosclerotic plaque progression and enhances plaque stability by inhibiting inflammatory responses, reducing the expression of matrix metalloproteinases and promoting macrophages from proinflammatory phenotype to anti-inflammatory phenotype[5].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Nud/nud mice are injected with A375R cells[4]
Dosage:
40, 80 mg/kg
Administration:
I.p. daily for two weeks
Result:
Led to an intermediate level of tumor growth suppression at dose of 40 mg/kg, and significant inhibition of A375R tumor growth at dose of 80 mg/kg. Well tolerated by healthy mice without significant signs of overt toxicity or weight loss.
分子量
266.29
Formula
C16H14N2O2
CAS 号
146535-11-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Gazit A, etm, al. Tyrphostins. 5. Potent inhibitors of platelet-derived growth factor receptor tyrosine kinase: structure-activity relationships in quinoxalines, quinolines, and indole tyrphostins. Comparative Study J Med Chem. 1996 May 24; 39(11): 2170-7.
[2]. Kovalenko M, et, al. Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation. Cancer Res. 1994 Dec 1; 54(23): 6106-14.
[3]. Tse KF, et, al. 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.
[4]. Li Y, et, al. 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.
[5]. Dong M, et, al. 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.
