Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Patent News

Novel 1,4-Dihydropyrido[2,3-B]Pyrazine-2,3-Dione Derivatives for Treating Cancer and Other Disorders Associated with KRAS Activity

Author(s): Surya K. De*

Volume 23, Issue 8, 2023

Published on: 29 December, 2022

Page: [979 - 980] Pages: 2

DOI: 10.2174/1871520623666221128110638

Price: $65

Abstract

This application describes the synthesis of new 1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione derivatives and methods of using these compounds as KRAS covalent inhibitors. This class of compounds is useful for treating cancer and other diseases associated with KRAS activity.

« Previous
Graphical Abstract

[1]
Addissie, Y.A.; Kotecha, U.; Hart, R.A.; Martinez, A.F.; Kruszka, P.; Muenke, M. Craniosynostosis and Noonan syndrome with KRAS mutations: Expanding the phenotype with a case report and review of the literature. Am. J. Med. Genet. A., 2015, 167(11), 2657-2663.
[http://dx.doi.org/10.1002/ajmg.a.37259] [PMID: 26249544]
[2]
Karachaliou, N.; Mayo, C.; Costa, C.; Magrí, I.; Gimenez-Capitan, A.; Molina-Vila, M.A.; Rosell, R. KRAS mutations in lung cancer. Clin. Lung Cancer, 2013, 14(3), 205-214.
[http://dx.doi.org/10.1016/j.cllc.2012.09.007] [PMID: 23122493]
[3]
Roman, M.; Hwang, E.; Sweet-Cordero, E.A. Synthetic vulnerabilities in the KRAS pathway. Cancers, 2022, 14(12), 2837.
[http://dx.doi.org/10.3390/cancers14122837] [PMID: 35740503]
[4]
Herbst, R.S.; Heymach, J.V.; Lippman, S.M. Lung cancer. N. Engl. J. Med., 2008, 359(13), 1367-1380.
[http://dx.doi.org/10.1056/NEJMra0802714] [PMID: 18815398]
[5]
Swanton, C.; Govindan, R. Clinical implications of genomic discoveries in lung cancer. N. Engl. J. Med., 2016, 374(19), 1864-1873.
[http://dx.doi.org/10.1056/NEJMra1504688] [PMID: 27168435]
[6]
Adderley, H.; Blackhall, F.H.; Lindsay, C.R. KRAS-mutant non-small cell lung cancer: Converging small molecules and immune checkpoint inhibition. EBioMedicine, 2019, 41, 711-716.
[http://dx.doi.org/10.1016/j.ebiom.2019.02.049] [PMID: 30852159]
[7]
Sartore-Bianchi, A.; Trusolino, L.; Martino, C.; Bencardino, K.; Lonardi, S.; Bergamo, F.; Zagonel, V.; Leone, F.; Depetris, I.; Martinelli, E.; Troiani, T.; Ciardiello, F.; Racca, P.; Bertotti, A.; Siravegna, G.; Torri, V.; Amatu, A.; Ghezzi, S.; Marrapese, G.; Palmeri, L.; Valtorta, E.; Cassingena, A.; Lauricella, C.; Vanzulli, A.; Regge, D.; Veronese, S.; Comoglio, P.M.; Bardelli, A.; Marsoni, S.; Siena, S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol., 2016, 17(6), 738-746.
[http://dx.doi.org/10.1016/S1470-2045(16)00150-9] [PMID: 27108243]
[8]
Roock, W.D.; Vriendt, V.D.; Normanno, N.; Ciardiello, F.; Tejpar, S. KRAS, BRAF, PIK3CA, and PTEN mutations: Implications for targeted therapies in metastatic colorectal cancer. Lancet Oncol., 2011, 12(6), 594-603.
[http://dx.doi.org/10.1016/S1470-2045(10)70209-6] [PMID: 21163703]
[9]
Rohatgi, A.; Govindan, R. Targeting KRAS G12C mutation in lung adenocarcinoma. Lung Cancer, 2022, 165, 28-33. Epub ahead of print
[http://dx.doi.org/10.1016/j.lungcan.2021.12.021] [PMID: 35066360]
[10]
Fakih, M.G.; Kopetz, S.; Kuboki, Y.; Kim, T.W.; Munster, P.N.; Krauss, J.C.; Falchook, G.S.; Han, S.W.; Heinemann, V.; Muro, K.; Strickler, J.H.; Hong, D.S.; Denlinger, C.S.; Girotto, G.; Lee, M.A.; Henary, H.; Tran, Q.; Park, J.K.; Ngarmchamnanrith, G.; Prenen, H.; Price, T.J. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): A prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol., 2022, 23(1), 115-124.
[http://dx.doi.org/10.1016/S1470-2045(21)00605-7] [PMID: 34919824]
[11]
Simanshu, D.K.; Nissley, D.V.; McCormick, F. RAS proteins and their regulators in human disease. Cell, 2017, 170(1), 17-33.
[http://dx.doi.org/10.1016/j.cell.2017.06.009] [PMID: 28666118]
[12]
Cox, A.D.; Fesik, S.W.; Kimmelman, A.C.; Luo, J.; Der, C.J. Drugging the undruggable RAS: Mission possible? Nat. Rev. Drug Discov., 2014, 13(11), 828-851.
[http://dx.doi.org/10.1038/nrd4389] [PMID: 25323927]
[13]
Cekani, E.; Epistolio, S.; Dazio, G.; Cefalì, M.; Wannesson, L.; Frattini, M.; Froesch, P. Molecular biology and therapeutic perspectives for K-Ras mutant non-small cell lung cancers. Cancers (Basel), 2022, 14(17), 4103.
[http://dx.doi.org/10.3390/cancers14174103] [PMID: 36077640]
[14]
Punekar, S.R.; Velcheti, V.; Neel, B.G.; Wong, K.K. The current state of the art and future trends in RAS-targeted cancer therapies. Nat. Rev. Clin. Oncol., 2022, 19(10), 637-655.
[http://dx.doi.org/10.1038/s41571-022-00671-9] [PMID: 36028717]
[15]
Boike, L.; Henning, N.J.; Nomura, D.K. Advances in covalent drug discovery. Nat. Rev. Drug Discov., 2022, 1-18.
[http://dx.doi.org/10.1038/s41573-022-00542-z] [PMID: 36008483]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy