Afatinib’s chemical name is (S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6 -yl)-4-(dimethylamino)but-2-enamide. It is a potent, irreversible dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Afatinib is the first irreversible ErbB family blocker. On July 12, 2013, the US Food and Drug Administration (FDA) announced that Afatinib has been approved for the treatment of advanced (metastatic) non-small cell lung cancer (NSCLC) patients.
Indication
Afatinib is a kinase inhibitor indicated as monotherapy 3 for the first-line Label treatment of (a) Epidermal Growth Factor Receptor (EGFR) TKI (tyrosine kinase inhibitor)-naive adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours have non-resistant EGFR mutations as detected by an FDA-approved test Label, and (b) adult patients with locally advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy Label,3.
Recently, as of January 2018, the US FDA approved a supplemental New Drug Application for Boehringer Ingelheim's Gilotrif (afatinib) for the first line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test 4. The new label includes data on three additional EGFR mutations: L861Q, G719X and S768I 4.
Associated Conditions
Metastatic Non-Small Cell Lung Cancer
Refractory, metastatic squamous cell Non-small cell lung cancer
TARGET: Epidermal growth factor receptor, Receptor tyrosine-protein kinase erbB-2, Receptor tyrosine-protein kinase erbB-4
ACTIONS: inhibitor
Synthesis
References:
1. WO0250043A1.
2. J. Med. Chem. 2009, 52, 6880–6888.
3. CN103755688A.
4. CN103965120A.
References:
1. US20050085495A1.
2. Bioorg. Med. Chem. 2013, 21, 7988-7998.
3. J. Org. Chem. 1986, 51, 616-620.
4. WO2007085638A1.
References:
1. CN103242303A.
2. WO2014183560A1.
3. CN103288808A.
References:
1. CN103254156A.
2. CN103254182A.
3. CN103254183A.
4. WO2014180271A1.
Clinical Trial Information
| NCT Number | Phase | Status | Date | Conditions | Sponsor/Collaborators |
| NCT02423525 | Recruiting | 2019-05-16 | Brain Cancer | Santosh Kesari | |
| NCT02372006 | Recruiting | 2019-05-13 | Neuroectodermal TumorsRhabdomyosarcoma | Boehringer Ingelheim | |
| NCT02780687 | Active, not recruiting | 2019-05-13 | Urologic Neoplasms | Boehringer Ingelheim | |
| NCT03157089 | Active, not recruiting | 2019-05-13 | Carcinoma, Non-Small-Cell Lung | Boehringer Ingelheim |
Literatures
| Publication Date | Title | Journal |
| 2017-01-01 | YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells. | PloS one |
| 2016-07-28 | Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers. | Journal of medicinal chemistry |
| 2016-03-15 | EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor. | Cancer research |
| 2015-09-01 | Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer. | The Lancet. Oncology |
| 2013-10-01 | Targeted therapies: Afatinib--new therapy option for EGFR-mutant lung cancer. | Nature reviews. Clinical oncology |
