tcsc0124 Gefitinib

Gefitinib is an inhibitor that specifically binds and inhibits the EGFR tyrosine kinase, with the IC₅₀ value of 2-37 nM in NR6wtEGFR cells.

IC50 & Target: IC50: 37 nM (Tyr1173 site, in NR6wtEGFR cells), 37 nM (Tyr992 site, in NR6wtEGFR cells)^[1]

In Vitro: Gefitinib (0.01-0.1 mM) results in increased phosphotyrosine load of the receptor, increased signalling to ERK and stimulation of proliferation and anchorage-independent growth, presumably by inducing EGFRvIII dimerisation in long-term exposure of EGFRvIII-expressing cells. On the other hand, gefitinib (1-2 mM) significantly decreases EGFRvIII phosphotyrosine load, EGFRvIII-mediated proliferation and anchorage-independent growth^[1]. Gefitinib (ZD1839) inhibits the monolayer growth of these EGF-driven untransformed cells with IC₅₀ of 20 nM^[2]. Gefitinib leads to an inhibition of CALU-3 and GLC82 cell proliferation, with an IC₅₀ of 2 μM^[3].

In Vivo: Gefitinib (150 mg/kg, p.o.) in conbination with Metformin induces a significant reduction in tumor growth in nude mice bearing H1299 or CALU-3 GEF-R cells that are grown subcutaneously as tumor xenografts^[3]. In irradiated rats, Gefitinib treatment augmentes lung inflammation, including inflammatory cell infiltration and pro-inflammatory cytokine expression, while Gefitinib treatment attenuates fibrotic lung remodeling due to the inhibition of lung fibroblast proliferation^[4].