IC50: 20 μM for PDGF receptor kinase in human bone marrow fibroblasts

AG-370 is a tyrphostin PDGFR inhibitor.

Protein tyrosine kinase inhibitors are potential antiproliferative agents for diseases caused by the hyperactivity of protein tyrosine kinases. Tyrphostins are a class of antiproliferative agents selectively inhibiting protein tyrosine kinases of key growth factors including epidermal growth factor or platelet-derived growth factor (PDGF) via blocking the phosphorylation of tyrosine residues.

In vitro: Previous study found that AG-370 inhibited PDGF receptor autophosphorylation and the tyrosine phosphorylation of intracellular protein substrates that coprecipitated with the PDGF receptor in digitonin-permeabilized fibroblasts and in intact fibroblasts. When compared with AG18, a potent EGF receptor blocker, AG370 was more efficient in inhibiting PDGF-induced proliferation of fibroblasts and phosphorylation of the intracellular protein substrates. Under the conditions in which AG370 could inhibit PDGF-induced mitogenesis and phosphorylation, AG18 did not alter [125I]PDGF internalization and enhance [125I]PDGF binding. These findings suggested that AG370 might have a therapeutic potential for treatment of diseases involving abnormal cellular proliferation induced by PDGF [1].

In vivo: Up to now, there is no animal in vivo data reported.

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] Bryckaert, M. C.,Eldor, A.,Fontenay, M., et al. Inhibition of platelet-derived growth factor-induced mitogenesis and tyrosine kinase activity in cultured bone marrow fibroblasts by tyrphostins. Experimental Cell Research 199, 255-261 (1992).