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Quinazoline is an organic compound with the formula C8H6N2. It is an aromatic heterocycle with a bicyclic structure consisting of two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring. It is a light yellow crystalline solid that is soluble in water. Also known as 1,3-diazanaphthalene, quinazoline received its name from being an aza derivative of quinoline. Though the parent quinazoline molecule is rarely mentioned by itself in technical literature, substituted derivatives have been synthesized for medicinal purposes such as antimalarial and anticancer agents. Quinazoline is a planar molecule. It is isomeric with the other diazanaphthalenes of the benzodiazine subgroup: cinnoline, quinoxaline, and phthalazine. Over 200 biologically active quinazoline and quinoline alkaloids are identified.
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Icotinib is a highly selective, first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Icotinib is approved for use in China as first-line monotherapy in patients with non-small-cell lung cancer with somatic EGFR mutations.
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T790M, also known as Thr790Met, is a gatekeeper mutation of the epidermal growth factor receptor (EGFR). The mutation substitutes a threonine (T) with a methionine (M) at position 790 of exon 20, affecting the ATP binding pocket of the EGFR kinase domain. Threonine is a small polar amino acid; methionine is a larger nonpolar amino acid. Rather than directly blocking inhibitor binding to the active site, T790M increases the affinity for ATP so that the inhibitors are outcompeted; irreversible covalent inhibitors such as neratinib can overcome this resistance.
Roy S. Herbst is an American oncologist who is the Ensign Professor of Medicine, Professor of Pharmacology, Chief of Medical Oncology, and Associate Director for Translational Research at Yale Cancer Center and Yale School of Medicine in New Haven, Connecticut.
References
- 1 2 "Daniel A. Haber". HHMI. Retrieved 10 November 2012.
- 1 2 "Daniel Haber, M.D., Ph.D." Retrieved 10 November 2012.
- ↑ Haber, DA; Buckler, AJ; Glaser, T; Call, KM; Pelletier, J; Sohn, RL; Douglass, EC; Housman, DE (Jun 29, 1990). "An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor". Cell. 61 (7): 1257–69. doi:10.1016/0092-8674(90)90690-g. PMID 2163761. S2CID 11931372.
- ↑ "MERIT Award Recipient: Daniel A. Haber, M.D., Ph.D." Retrieved 10 November 2012.
- ↑ Lynch, Thomas J.; Bell, Daphne W.; Sordella, Raffaella; Gurubhagavatula, Sarada; Okimoto, Ross A.; Brannigan, Brian W.; Harris, Patricia L.; Haserlat, Sara M.; Supko, Jeffrey G.; Haluska, Frank G.; Louis, David N.; Christiani, David C.; Settleman, Jeff; Haber, Daniel A. (20 May 2004). "Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib" (PDF). New England Journal of Medicine. 350 (21): 2129–2139. doi:10.1056/NEJMoa040938. PMID 15118073.
- ↑ Sordella, R; Bell, DW; Haber, DA; Settleman, J (Aug 20, 2004). "Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways". Science. 305 (5687): 1163–7. Bibcode:2004Sci...305.1163S. doi:10.1126/science.1101637. PMID 15284455. S2CID 34389318.
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