Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery


ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Review Article

The Patent Landscape of BRAF Target and KRAS Target

Author(s): Hai-Long Zhang* and Yongxia Li

Volume 18, Issue 4, 2023

Published on: 22 December, 2022

Page: [495 - 505] Pages: 11

DOI: 10.2174/1574892818666221207091329

Price: $65


Background: KRAS and BRAF targets are involved in the epidermal growth factor receptor pathway. KRAS and BRAF targets are the most frequent driver mutations in cancer.

Objective: The objective of the study was to present the recent developments in the KRAS target and the BRAF target.

Methods: KRAS target and BRAF target were analyzed by US patent analysis. All US granted patent documents from January 2002 to November 2021 were retrieved.

Results: The results showed both KRAS and BRAF targets to be attractive targets for developing anticancer drugs. The technology of RNA interference has been developed for drug discovery related to the KRAS target. Our study indicates that the structural screening of inhibitors between the KRAS target and the BRAF target should be an inverse option.

Conclusion: The chemical structures of inhibitors of BRAF target exhibited a unique classification of C07D405. The inhibitors of BRAF target could be used for the treatment of various cancers. However, the inhibitors of KRAS target did not show this feature. The present study provides new insight into drug discovery involving KRAS and BRAF targets.

Keywords: KRAS, BRAF, targeted drugs, patent, patent landscape, cancer.

Boch C, Kollmeier J, Roth A, et al. The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): Routine screening data for central Europe from a cohort study. BMJ Open 2013; 3(4): e002560.
[] [PMID: 23558737]
Gorukmez O, Yakut T, Gorukmez O, Sag SO, Karkucak M, Kanat O. Distribution of KRAS and BRAF mutations in metastatic colorectal cancers in Turkish patients. Asian Pac J Cancer Prev 2016; 17(3): 1175-9.
[] [PMID: 27039744]
Bylsma LC, Gillezeau C, Garawin TA, et al. Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis. Cancer Med 2020; 9(3): 1044-57.
[] [PMID: 31856410]
Bennani B, Gilles S, Fina F, et al. Mutation analysis of BRAF exon 15 and KRAS codons 12 and 13 in Moroccan patients with colorectal cancer. Int J Biol Markers 2010; 25(4): 179-84.
[] [PMID: 21161938]
Riely GJ, Kris MG, Rosenbaum D, et al. Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res 2008; 14(18): 5731-4.
[] [PMID: 18794081]
Imamura Y, Lochhead P, Yamauchi M, et al. Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: Cohort study and literature review. Mol Cancer 2014; 13(1): 135.
[] [PMID: 24885062]
Vu Thi MT, Le VT, Huynh QH, Nguyen MD. KRAS gene mutation in patients with primary colorectal cancer. Acta Medica 2019; 50(1): 20-5.
Demiray A, Yaren A, Karagenç N, et al. The frequency of EGFR And KRAS mutations in the Turkish population with non-small cell lung cancer and their response to erlotinib therapy. Balkan J Med Genet 2018; 21(2): 21-6.
[] [PMID: 30984520]
Bacchi CE, Ciol H, Queiroga EM, Benine LC, Silva LH, Ojopi EB. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients. Clinics 2012; 67(5): 419-24.
[] [PMID: 22666783]
Wang H, Wang L, Zhang Y, Wang J, Deng Y, Lin D. Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth. Cancer Cell Int 2016; 16(1): 9.
[] [PMID: 27570490]
Sithanandam G, Kolch W, Duh FM, Rapp UR. Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies. Oncogene 1990; 5(12): 1775-80.
[PMID: 2284096]
Sithanandam G, Druck T, Cannizzaro LA, Leuzzi G, Huebner K, Rapp UR. B-Raf and a B-Raf pseudogene are located on 7q in man. Oncogene 1992; 7(4): 795-9.
[PMID: 1565476]
Tan YH, Liu Y, Eu KW, et al. Detection of BRAF V600E mutation by pyrosequencing. Pathology 2008; 40(3): 295-8.
[] [PMID: 18428050]
Namba H, Nakashima M, Hayashi T, et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab 2003; 88(9): 4393-7.
[] [PMID: 12970315]
Li L. Inhibitors of KRAS G12C mutant proteins. Patent US10730867B2, 2020.
Wurz RP, Victor J, Amegadzie A, et al. KRAS G12C inhibitors and methods of using the same. Patent US11045484B2, 2021.
Lanman B A, Chen J. KRAS G12C inhibitors and methods of using the same. Patent US10519146B2, 2019.
Detmer J, Uzgiris A, Ying A. Oligonucleotides and methods for detecting KRAS and PIK3CA mutations Patent US8940486B2, 2015.
Brown Bd. Methods and compositions for the specific inhibition of KRAS by asymmetric double-stranded RNA Patent US9809819B2, 2017.
Springer C J. Pyrido2,3-Bpyrazin-8-substituted compounds and their use. Patent US9155737B2, 2015.
Springer C J, Marais R, Girotti R, Niculescu-Duvaz D, Niculescu-Duvaz I. 1-(5-tert-butyl-2-aryl-pyrazol-3-yl)-3-2-fluoro-4-(3-oxo-4H-pyrido2,3-b pyrazin-8-yl)oxyphenylurea derivatives as RAF inhibitors for the treatment of cancer. Patent US9725447B2, 2017.
Dumble M, Kumar R, Laquerre S, Lebowitz P. Pharmaceutical combination of MEK inhibitor and B-Raf inhibitors. Patent US8952018B2, 2015.
Dumble M, Gilmer T, Kumar R, Lebowitz PF, Morris SR, Laquerre S. Combination of inhibitor of B-Raf and an inhibitor of Akt in the treatment of cancer. Patent US8835450B2, 2014.
Zhang HL, Li Y. Recent trend for EGFR-based and ALK-based targets: A patent analysis. Recent Patents Anticancer Drug Discov 2021; 16(3): 298-311.
[] [PMID: 33847258]
The U.S. Food and Drug Administration 2020. Available from:

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