Tyrphostin AG 1296

Tyrphostin AG 1296 is a selective inhibitor of platelet-derived growth factor receptor (PDGFR) with IC50 value of 0.3μM-0.5μM [1].

Tyrphostin AG 1296 is an ATP-competitive inhibitor of PDGFR. It binds to PDGFR, causing a conformational change at the ATP-binding site. In the in vitro assay, it potently inhibits the ligand-induced autophosphorylation of PDGF receptor in Swiss 3T3 cell membranes. Tyrphostin AG 1296 does not affect the EGF receptor when the concentration is up to 100μM. Tyrphostin AG 1296 also inhibits the mitogenesis induced by PDGF but not EGF or insulin. It reversibly inhibits PDGF-induced DNA synthesis with a mean IC50 value of 1.5μM. Besides that, tyrphostin AG 1296 inhibits PDGF-induced cell growth with IC50 value of 3.2μM in Swiss 3T3 cells [1, 2].

References:
[1] Kovalenko M, Gazit A, Böhmer A, et al. Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation. Cancer Research, 1994, 54(23): 6106-6114.
[2] Kovalenko M, Rönnstrand L, Heldin C H, et al. Phosphorylation site-specific inhibition of platelet-derived growth factor β-receptor autophosphorylation by the receptor blocking tyrphostin AG1296. Biochemistry, 1997, 36(21): 6260-6269.

Additive effect by combination of Akt inhibitor, MK-2206, and PDGFR inhibitor, tyrphostin AG 1296, in suppressing anaplastic thyroid carcinoma cell viability and motility.[Pubmed:24665203]

Onco Targets Ther. 2014 Mar 14;7:425-32.

The phosphatidylinositol-3-kinase/Akt pathway and receptor tyrosine kinases regulate many tumorigenesis related cellular processes including cell metabolism, cell survival, cell motility, and angiogenesis. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with no effective systemic therapy. It has been shown that Akt activation is associated with tumor progression in ATC. Here we observed the additive effect between an Akt inhibitor (MK-2206) and a novel platelet-derived growth factor receptor inhibitor (Tyrphostin AG 1296) in ATC therapy. We found an additive effect between MK-2206 and Tyrphostin AG 1296 in suppressing ATC cell viability. The combination of MK-2206 and Tyrphostin AG 1296 induces additive apoptosis, additive suppression of the Akt signaling pathway, as well as additive inhibition of cell migration and invasion of ATC cells. Furthermore, the combination of MK-2206 and Tyrphostin AG 1296 induced additive suppression of ATC tumor growth in vivo. In summary, our studies suggest that the combination of Akt and receptor tyrosine kinase inhibitors may be an efficient therapeutic strategy for ATC treatment, which might shed new light on ATC therapy.

Tyrphostin AG 1296 induces glioblastoma cell apoptosis in vitro and in vivo.[Pubmed:26788146]

Oncol Lett. 2015 Dec;10(6):3429-3433.

Glioblastoma is the most common type of malignant human brain tumor. Currently available chemotherapies for glioblastoma focus on targeting tyrosine kinases. However, the existing inhibitors of tyrosine kinases have not produced the therapeutic outcomes that were anticipated. In order to investigate the viability alternative chemotherapeutic agents in this disease, the present study examined the anticancer effects of Tyrphostin AG 1296, focusing on its involvement in apoptosis in glioblastoma cells. The study aimed to identify whether Tyrphostin AG 1296 affects glioblastoma cell growth by inducing cell apoptosis. To achieve this, cell viability, propidium iodide analysis and cell invasion assay were used to measure cell growth, cell apoptosis and cell migration of human glioblastoma cells. The results showed that Tyrphostin AG 1296 treatment reduced cell viability and suppressed migration of human glioblastoma cells. It was also demonstrated that Tyrphostin AG 1296 induced cell apoptosis in vitro. Finally, Tyrphostin AG 1296 was also shown to significantly inhibit the growth of glioblastoma cells and to increase tumor cell apoptosis in vivo. These findings suggest that Tyrphostin AG 1296 induces apoptosis, thereby reducing cell viability and capacity for migration of glioblastoma cells.