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Synonyms: compound 47 [PMID: 27433829] | EGF-816 | EGF816
Compound class:
Synthetic organic
Comment: EGF816 is an irreversible and selective inhibitor of EGFRs harbouring gatekeeper T790M, and sensitising L858R mutations, whilst sparing the wild-type receptor (such compounds are termed third generation EGFR tyrosine kinase inhibitors) [3]. It has been developed to overcome acquired resistance to, and side-effect liabilities of first and second generation EGFR inhibitors in non-small-cell lung cancer (NSCLC). Small-molecule EGFR T790M inhibitors and the development of novel compounds in the discovery pipeline are reviewed by Song et al. (2016) [5].
EGF816 is claimed in Novartis' patent WO2015085482 [4], where it is named (R,E)-N-(7-chloro-l-(l-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-lH-benzo[d]imidazol-2-yl)-2-methylisonicotinamide, which resolves to the IUPAC name presented here. Preclinical characterisation is reported in [1]. 
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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| References |
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1. Jia Y, Juarez J, Li J, Manuia M, Niederst MJ, Tompkins C, Timple N, Vaillancourt MT, Pferdekamper AC, Lockerman EL et al.. (2016)
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 Res, 76 (6): 1591-602. [PMID:26825170] |
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2. Kobayashi Y, Mitsudomi T. (2016)
Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy. Cancer Sci, 107 (9): 1179-86. [PMID:27323238] |
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3. Lelais G, Epple R, Marsilje TH, Long YO, McNeill M, Chen B, Lu W, Anumolu J, Badiger S, Bursulaya B et al.. (2016)
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. J Med Chem, 59 (14): 6671-89. [PMID:27433829] |
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4. Mao L, Pan W, Wang X, Zhang Y, Li R, Waykole L, Sethuraman V. (2015)
Egfr inhibitor forms. Patent number: WO2015085482. Assignee: Novartis Ag. Priority date: 10/12/2013. Publication date: 18/06/2015. |
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5. Song Z, Ge Y, Wang C, Huang S, Shu X, Liu K, Zhou Y, Ma X. (2016)
Challenges and Perspectives on the Development of Small-Molecule EGFR Inhibitors against T790M-Mediated Resistance in Non-Small-Cell Lung Cancer. J Med Chem, 59 (14): 6580-94. [PMID:26882288] |
