Protein tyrosine kinase (PTK) inhibitors are potential antiproliferative agents for diseases caused by the hyperactivity of PTKs. Tyrphostins are a class of antiproliferative compounds which selectively inhibit PTKs of key growth factors such as epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) by blocking the phosphorylation of specific tyrosine residues. AG-370 is a selective inhibitor of PDGF receptor kinase with an IC50 value of 20 μM in human bone marrow fibroblasts. It displays comparatively weak inhibition of the EGF receptor (IC50 = 820 μM).
ChEBI: AG-370 is a member of indoles.
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].
20 μm for pdgf receptor kinase in human bone marrow fibroblasts
[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).
