Next generation tyrosine kinase inhibitor (TKI): afatinib.
Afatinib is a recently introduced new tyrosine kinase inhibitor, approved by the USFDA on July 12, 2013. Afatinib is marketed under the trade name Gilotrif and developed by Boehringer Ingelheim GmbH. It is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) carrying EGFR exon 19 deletions or exon 21 (L858R) mutations. Afatinib is a covalent, irreversible inhibitor of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2) and HER4. Chemically afatinib is a 4-anilinoquinazoline derivative, having an acrylamide warhead. Gilotrif is the formulation of Afatinib di-meleate salt. Presently, afatinib has been approved in the USA, the European Union, Taiwan and Mexico. In this review, we have summarized the chemical characterization of afatinib, its synthesis, patent status, marketed formulation, available crystalline form and current clinical trials.
Suresh
S
Kumar
Department of Chemistry, Shrimant Madhavrao Scindia, Government Model Science College, Jhansi Road, Gwalior, Madhya Pradesh, PIN No. 474001, India. riteshagrawalip@gmail.com.
Ritesh
R
Agrawal
D000077716:Afatinib; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D011505:Protein-Tyrosine Kinases