Product information

Gefitinib Basic information

Anti-tumor targeted therapy Pharmacokinetic Usage Adverse reactions

Product Name:	Gefitinib
Synonyms:	IRESSA;GEFITINIB;AKOS 91371;n-(3-chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine;N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine;ZD 1839;4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-;Gefitinib(TINIBS)
CAS:	184475-35-2
MF:	C22H24ClFN4O3
MW:	446.9
EINECS:
Product Categories:	Active Pharmaceutical Ingredients;Gefitinib;Molecular Targeted Antineoplastic;Intermediates & Fine Chemicals;Pharmaceuticals;Pharmaceutical intermediate;APIs;IRESSA;Anti-cancer&immunity;API;Inhibitors
Mol File:	184475-35-2.mol

Gefitinib Chemical Properties

mp	119-1200C
storage temp.	Store at RT
CAS DataBase Reference	184475-35-2(CAS DataBase Reference)

 

Gefitinib Usage And Synthesis

Anti-tumor targeted therapy	Gefitinib is a kind of high specificity anti-tumor targeted therapy drugs developed by Astrazeneca Company (UK) and is the first molecular targeted-drug used in the treatment of non-small cell lung cancer. It takes effect by selectively inhibit the signalling transduction pathway of epidermal growth factor receptor tyrosine kinase (EGFR - TK). Epidermal growth factor (EGF) is a kind of polypeptide with a relative molecular mass of 6.45 x 103. It can bind to the epidermal growth factor receptor (EGFR) located on the targeted cell membrane to play its biological role. EGFR is a kind of tyrosine kinase (TK) type receptor which can promote the TK activation inside the body when binding to the EGF, and thus resulting in the auto-phosphorylation of the tyrosine residues of the receptor, providing continuous division signals to the cell to boost the cell proliferation and differentiation. EGFR is also rich in human tissue and has high expression level in malignant tumor. Gefitinib can block the proliferation, metastasis of the tumor and angiogenesis by blocking the EGFR signaling pathways on the cell surface, and can also induce the apoptosis of tumor cells.  In August 2002, gefitinib is first used as the first-line therapy for treating non-small cell lung cancer and entered into market in Japan with commodity called “Yi Rui Sha”. In May 2003, the U.S. food and drug administration (FDA) approved gefitinib to become the third-line single treatment drug for patients with advanced non-small cell lung cancer which has received no effective treatment result through platinum anticancer drugs and docetaxel chemotherapy. Currently, it has been approved by Australia, Japan, Argentina, Singapore and South Korea and some other countries for application in the treatment of advanced non-small cell lung cancer. On February 28, 2005, China's food and drug administration approved gefitinib to be applied to the treatment of tropical advanced or metastatic non-small cell lung cancer (NSCLC) which has received chemotherapy before. However, at present, it has not yet been approved as first-line treatment of advanced NSCLC. On July 1, 2009, the drug administration agency of the European Union has officially approved gefitinib for being used as first-line, second-line as well third-line treatment on the tropical advanced or metastatic non-small cell lung cancer of adult with the EGFR gene mutation.
Pharmacokinetic	It is effective through oral administration with a low metabolism rate after the oral absorption. A single oral administration of 250 mg has a bioavailability being close to 60%. During the medication, the area under the curve (AUC) was dose related. After administration of 1 times per day, it reaches steady-state blood drug concentration after the treatment of 7 ~ 10 days with the plasma concentration peak occurring at 3 ~ 7 hours after the administration, then the blood drug concentration gradually reduces in two phase (half-life: 12 ~ 58 hours with average time of 28 hours), and is characterized by dose dependent pharmacokinetic which means that AUC and Cmax increase in proportion to each other with multiple dosing. However, when taking it together with food, its Cmax and AUC did not significantly reduced. It has a plasma protein bind rate being nearly 90%. Gefitinib is metabolized in liver by multiple and complicated metabolic pathways. The enzyme which participates in its oxidative metabolism is mainly the CYP3A4 in the cytochrome P450 enzyme system whose major metabolites are O- dimethyl substance. The metabolites have nothing to do with the pharmacology of the prototype drug. The prototype drugs and most of the metabolites are mainly excreted through the biliary drainage and are discharged out of the body through feces. The metabolites excreted through urinary excretion only accounts for lower than 4% of the dosage. The above information is edited by the chemicalbook of Dai Xiongfeng.
Usage	Gefitinib is a kind of selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. The recommended treatment dose of adult is 250 mg of (1 tablet) with 1 time per day through orally administration, either in empty stomach or together with food.  If you have difficulty in swallowing, you can disperse the tablets into a half cup of drinking water (non-carbonated beverages). Make sure to avoid using other kinds of liquid. Cast tablets into the water and stir until the complete dispersion of the tablet in the water (takes about 10 minutes) without the necessity of crushing. Immediately drink the liquid, and use half glass of water to rinse the cup, drink again. Alternatively, you can also administrate this drug solution through the nose - stomach tube. There is no necessity in adjusting the administrated dosage of the drug: age, weight, gender, race, renal function, and moderate to severe liver function dysfunction caused by hepatic metastasis.  Dose adjustment: when patients can't tolerate the diarrhea or skin adverse reactions, you can tackle this issue through short-term suspension (up to 14 days) of the treatment and then restore the dose of 250 mg per day.
Adverse reactions	It has a better tolerability with most adverse reaction being minor and reversible, and is totally different from typical adverse reactions of cytotoxic drugs. Common adverse reactions include diarrhea, nausea, rashes, acne, vomiting and weakness with the incidence being over 20%. The ratio of patents who stops the treatment because of the adverse drug reactions is only 1%. Sometimes acute interstitial pneumonia can happen occasionally which can even cause death of some patients. Therefore, if enhanced respiratory symptoms such as shortness of breath, cough and fever happen in the patients, should immediately discontinue the treatment, and find out whether it is interstitial pneumonia. Gefitinib is not suitable for applied to women during pregnancy. Lactation women should stop breastfeeding during the treatment.
Chemical Properties	Light-Yellow Crystalline Powder
Usage	Gefitinib (Iressa, 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.
Usage	Gefitinib is an antineoplastic.
Biological Activity	Orally active, selective inhibitor of EGFR tyrosine kinase (IC 50 = 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 bearing a range of human xenografts.

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