[CAS NO. 146535-11-7] TyrphostinAG1296
PRODUCTS SPECIFICATIONS [146535-11-7]
DESCRIPTION [146535-11-7]
Overview
| MDL | MFCD00270913 |
|---|---|
| Molecular Weight | 266.29 |
| Molecular Formula | C16H14N2O2 |
| SMILES | COC1=C(OC)C=C2N=CC(C3=CC=CC=C3)=NC2=C1 |
1 Publications Citing Use of MCE
Summary
Tyrphostin AG1296 is a potent and selective inhibitor of platelet-derived growth factor receptor (PDGFR) , with an IC 50 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 IC 50 in the micromolar range [1] [2] [3] .
IC50 & Target
|
PDGFRα |
PDGFRβ |
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]
.
MCE 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. |
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]
.
MCE 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 33.33 mg/mL ( 125.16 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.7553 mL | 18.7765 mL | 37.5530 mL |
| 5 mM | 0.7511 mL | 3.7553 mL | 7.5106 mL |
| 10 mM | 0.3755 mL | 1.8777 mL | 3.7553 mL |
References
- [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.