|Selective EGFR inhibitor
......by AOBIOUS INC
|Gefitinib is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor and has been shown to increase phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in HaCaT cells. The Gefitinib selective inhibitor of EGFR tyrosine kinase (IC50 = 23 - 79 nM). Shows minimal activity against ErbB2, KDR, c-flt, PKC, MEK and ERK-2. Blocks EGFR autophosphorylation and inhibits tumor growth in mice.
......by Affix Scientific
|<p>Gefitinib, also known as ZD1839 or Iressa, is a potent and orally-bioavailable small-molecule inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase with 50% inhibition concentration IC<sub>50</sub> values of 0.033 μM and 0.027 μM in A431 membrane prep and baculovirus lysate respectively. Gefitinib binds to the kinase ATP binding site of EGFR interfering with the binding of adenosine triphosphate, which suppresses the EGFR tyrosine kinase activity and resultant signal transduction of EGFR. Gefitinib exhibits anti-angiogenic activities in a wide range of human tumor types, including head and neck, prostate, breast, ovarian, colon, small-cell lung and non-small-cell lung cancer. Moreover, geftinib has also been found to reduce proliferation, induce cell cycle arrest and increase apoptosis.</p>
<p><em>M. Ranson and S. Wardell. Gefitinib, a novel, orally administered agent for the treatment of cancer. Journal of Clinical Pharmacy and Therapeutics (2004) 29, 95-103</em></p>
<p><em>Joachim Von Pawel. Gefitinib (Iressa, ZD1839): a novel targeted approach for the treatment of solid tumors. Bull Cancer 2004; 91(5): E70-E76</em></p>
......by Apexbio Technology LLC
|EGFR tyrosine kinase inhibitor that binds to the ATP-binding site of the enzyme. The functions of the EGFR tyrosine kinase in activating the Ras signal transduction cascade and malignant cell growth are thus inhibited. It has been shown that a mutation in the EGFR tyrosine kinase domain is responsible for activating anti-apoptotic pathways in gefitinib-sensitive non-small cell lung cancers. These mutations tend to increase sensitivity to tyrosine kinase inhibitors including gefitinib and erlotinib. The adenocarcinoma subset of non-small cell lung cancer histologies often have these mutations, which are commonly found in Asians, women, and non-smokers. Pao, W., et al. "EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib." Proc. Natl. Acad. Sci. USA 101: 13306-13311 (2004). Sordella, R., et al. "Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways." Science 305: 1163-1167 (2004). The IC50 values for gefitinib for inhibiting HT-29 and LoVo cell growth were 23.6 - >100 µM and 7.3 - 48.5 µM, respectively, when the exposure times are from 18 hours to 3 days. A time-dependent reduction in IC50 was observed for gefitinib, with the IC50 after 3 days of exposure being 4-8 fold less after 18 hours of exposure. Azzariti, A., et al. "Prolonged exposure of colon cancer cells to the epidermal growth factor receptor inhibitor gefitinib (Iressa™) and to the antiangiogenic agent ZD6474: Cytotoxic and biomolecular effects." World J. Gastroenterol. 12: 5140-5147 (2006). Gefitinib was found to be a potent inhibitor of EGFR kinase (Ki = 0.40 nM), but much weaker against ErbB-2 kinase (Ki = 870 nM) and ErbB-4 kinase (Ki = 1.1 µM). Wood, E.R., et al. "A Unique Structure for Epidermal Growth Factor Receptor Bound to GW572016 (Lapatinib), Relationships among Protein Conformation, Inhibitor Off-Rate, and Receptor Activity in Tumor Cells." Cancer Res. 64: 6652-6659 (2004). The IC50 of gefitinib for cells grown in the absence (IC50 = 8.8 µM) of EGF is >100-fold weaker than that in the presence (IC50 = 0.054 µM) of EGF. Gefitinib selectively inhibited EGF-stimulated growth of HUVECs (IC50 = 0.03 - 0.1 µM) compared with FGF- or VEGF-stimulated growth (IC50 = 1 - 3 µM for both). Enzyme kinetic studies were used to determine the characteristics of gefitinib inhibition of EGFR tyrosine kinase. Gefitinib is a competitive inhibitor with respect to ATP (Ki = 2.1 nM) when the peptide substrate concentration was fixed at 2 mM (6-fold higher than the Km) and the ATP concentration was varied. Gefitinib showed noncompetitive kinetics (Ki = 15.0 nM) when the ATP concentration was 50 µM (6-fold higher than the Km) and the peptide concentration was varied. Wakeling, A.E., et al. "ZD1839 (Iressa), An Orally Active Inhibitor of Epidermal Growth Factor Signaling with Potential for Cancer Therapy." Cancer Res. 62: 5749-5754 (2002).
......by LC Laboratoies
|Gefitinib(ZD1839) is an EGFR inhibitor, which interrupts signaling through the epidermal growth factor receptor (EGFR) in target cells. Therefore, it is only effective in cancers with mutated and overactive EGFR.
IC50 Value: 37 nM (Tyr1173-NR6wtEGFR cells); 26 nM (Tyr1173 -NR6W cells) 
in vitro: Gefitinib effectively inhibits all tyrosine phosphorylation sites on EGFR in both the high and low-EGFR-expressing cell lines including NR6, NR6M and NR6W cell lines. The phosphorylation sites Tyr1173 and Tyr992 are less sensitive requiring higher concentrations of Gefitinib for inhibition. Gefitinib effectively blocks the phosphorylation of PLC-γ, with IC50 of 27nM, in NR6W cells. The NR6wtEGFR and NR6M cell lines has low levels of PLC-γ phosphorylation but the level in the NR6M cell line is more resistant to inhibition by Gefitinib with IC50 of 43 nM and 369 nM, respectively. Gefitinib inhibits Akt phosphorylations, with IC50 of 220 and 263nM, in the low-EGFR- and -EGFRvIII-expressing cell lines, respectively. Gefitinib in the dose range from 0.1 to 0.5μM significantly facilitates, rather than abrogates, colony formation of NR6M cells. However, at a concentration of 2 μM Gefitinib completely blocks NR6M colony formation. Gefitinib rapidly and in a dose-dependent manner inhibits EGFR and ERK phosphorylation up to 72 hours after EGF stimulation in both the high- and low-EGFR-expressing cell lines . Gefitinib is the monolayer growth of these EGF-driven untransformed MCF10A cells with an IC50 of 20 nM . The combination of metformin with gefitinib induced a strong antiproliferative and proapoptotic effect in NSCLC cell lines that harbored wild-type LKB1 gene .
in vivo: Gefitinib treatment increased the infiltration of inflammatory cells, which produced more pro-inflammatory cytokines (IL-6, IL-1β), in the lungs of the irradiated rats on days 15 and 57, while gefitinib treatment reduced collagen content of the lungs in irradiated rats and decreased proliferation and EGFR expression in the lung fibroblasts from irradiated rats on day 57 . SN-38 and its glucuronide after irinotecan (50 or 100 mg/kg) was orally administered with or without gefitinib 100 mg/kg to rats .
Toxicity: Three volunteers experienced adverse events (AEs) that were considered possibly related to gefitinib (pruritus and dry skin), and 6 volunteers experienced procedure-related AEs (cannula-site reaction and rhinorrhea) .
Clinical trial: Third-line Treatment of Gefitinib in NSCLC Patients. Phase 1
......by MedChemexpress Co., Ltd.
|Gefitinib (ZD-1839) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively.
......by Selleck Chemicals LLC
|Gefitinib (originally coded ZD1839) is a drug used in the treatment of certain types of cancer. Acting in a similar manner to erlotinib (marketed as Tarceva), gefitinib selectively targets the mutant proteins in malignant cells. It is marketed by AstraZeneca under the trade name Iressa.
......by Target Molecule Corp.