An updated patent review of VEGFR-2 inhibitors (2017-present)

References

• Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407(6801):249–257.
   PubMed Web of Science ®Google Scholar
• Benjamin LE, Bergers G. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3(6):401–410.
   PubMed Web of Science ®Google Scholar
• Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis. 2000;21(3):505–515.
   PubMed Web of Science ®Google Scholar
• Lainakis G, Bamias A. Targeting angiogenesis in renal cell carcinoma. Curr Cancer Drug Targets. 2008;8(5):349–358.
   PubMed Web of Science ®Google Scholar
• Lee CH, Motzer RJ. Kidney cancer in 2016: the evolution of anti-angiogenic therapy for kidney cancer. Nat Rev Nephrol. 2017;13(2):69–70.
   PubMed Web of Science ®Google Scholar
• Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005;69(3):4e10.
   Google Scholar
• Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23(5):1011–1027.
   PubMed Web of Science ®Google Scholar
• Otrock ZK, Makarem JA, Shamseddine AI. Vascular endothelial growth factor family of ligands and receptors: review. Blood Cell Mol Dis. 2007;38: 258–268.
   PubMed Web of Science ®Google Scholar
• Gotink KJ, Verheul HMW. Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis. 2010;13(1):1–14.
   PubMed Web of Science ®Google Scholar
• Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer. 2002;2(10):727–739.
   PubMed Web of Science ®Google Scholar
• Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors: a 2020 update. Pharmacol Res. 2020;152:104609.
   PubMed Web of Science ®Google Scholar
• Modi SJ, Kulkarni VM. Vascular endothelial growth factor receptor (VEGFR-2)/KDR inhibitors: medicinal chemistry perspective. Med Drug Discov. 2009. DOI:https://doi.org/10.1016/j.medidd.2019.100009
   Google Scholar
• Peng FW, Liu DK, Zhang QW, et al. VEGFR-2 inhibitors and the therapeutic applications thereof: a patent review (2012–2016). Expert Opin Ther Pat. 2017 Sep; 27(9):987–1004.
   PubMed Web of Science ®Google Scholar
• Jin Y, Lin J, Zhang J, et al. Preparation of N-substituted benzylidene pyrrolidinediones as VEGFR-2 inhibitors. Faming Zhuanli Shenqing. CN 106565585 A 20170419. 2017.
   Google Scholar
• Zhang J, Wang J, Pan X, et al. Diaryl urea compound with antitumor activity, preparation method and application thereof. Faming Zhuanli Shenqing. CN 106748991 A 20170531. 2017.
   Google Scholar
• He L, Zhang J, Wang J, et al. Diaryl urea compounds with antitumor activity, preparation method and application thereof. Faming Zhuanli Shenqing. CN 106748990 A 20170531. 2017.
   Google Scholar
• Walters I, Birch L, Collingwood SP, et al. Preparation of indole derivatives and their use as protein kinase inhibitors for the treatment of fibrosis. PCT Int. Appl. WO 2017153748 A1 20170914. 2017.
   Google Scholar
• Li J, Zhang Q, Lu B, et al. Preparation of sulfonylaniline pyrimidine derivatives used as antitumor drugs. Faming Zhuanli Shenqing. CN 110386901 A 20191029. 2019.
   Google Scholar
• Meng F, Liang J, Yang S, et al. Pyrimidine derivative useful in treatment of cancer and its preparation. Faming Zhuanli Shenqing. CN 106674136 A 20170517. 2017.
   Google Scholar
• Ye T, Lu X, Yu G, et al. Preparation of benzamides and pyridones useful as VEGFR-2 inhibitors. Faming Zhuanli Shenqing. CN 106496107 A 20170315. 2017,
   Google Scholar
• Bannen LC, Jiang F, Tso K, et al. Preparation of substituted N-[(quinolin-4-yl)-phenyl]-N’-phenylcyclopropane-1,1-dicarboxamides and analogs for the treatment of Axl and Mer receptor tyrosine kinase-dependent disorders. PCT Int. Appl. WO 2020154610 A1 20200730. 2020.
   Google Scholar
• Liu B, Qian X, Wang Y, et al. Tyrosine kinase inhibitor and its application in treatment of cancer. Faming Zhuanli Shenqing. CN 108358839 A 20180803.2018.
   Google Scholar
• Zhang Z, Wang X, Zhang X, et al. Quinolinyl-substituted carboxylic acid compound or pharmaceutically acceptable salt thereof, pharmaceutical composition thereof, and use thereof. PCT Int. Appl. WO 2018072614 A1 20180426. 2018.
   Google Scholar
• Horn G. Preparation of cabozantinib derivatives as multi-tyrosine kinase inhibitors for treatment of intraocular diseases. U.S. US 10464902 B1 20191105. 2019.
   Google Scholar
• Shan Y, Hu S, Dong Y, et al. Preparation of chalcone-based quinazolinone compound from isovanillin as multi-target RTKs inhibitors for anti-tumor drugs. Faming Zhuanli Shenqing. CN 110903253 A 20200324. 2020.
   Google Scholar
• Wu X, Fu Y, Wang Y, et al. Preparation of 1-(2-tetrahydropyran)-1H-pyrazolo[3,4-d]pyrimidine compounds as antitumor agents. Faming Zhuanli Shenqing. CN 106496232 A 20170315. 2017.
   Google Scholar
• Zhao L, Gou X. Purine series derivative and its preparation method and application as antitumor agents. Faming Zhuanli Shenqing. CN 109384788 A 20190226. 2019.
   Google Scholar
• Marshall AJ, Buchanan CM, Rewcastle GW, et al. Tricyclic heterocyclic derivatives as CSF-1R inhibitors and their preparation. PCT Int. Appl. WO 2018083635 A2 20180511. 2018.
   Google Scholar
• Zhang Q, Yu S, Wang Z, et al. Dioxazoline compound, preparation method therefor, and uses thereof. PCT Int. Appl. WO 2019154133 A1 20190815. 2019.
   Google Scholar
• Zhang Q, Yu S, Wang Z, et al. Process for preparation and application of urea-substituted aromatic ring-linked dioxazoline compound. PCT Int. Appl. WO 2019154132 A1 20190815. 2019.
   Google Scholar
• Zhang Q, Zhang H, Yang L, et al. Preparation of urea-substituted aromatic ring-linked dioxane[2.3-f]quinazoline and dioxane[2,3-f]quinoline derivatives useful as tyrosine kinase inhibitors. PCT Int. Appl. WO 2018157730 A1 20180907. 2018.
   Google Scholar
• Lv W, Zhang Q, Xiao D, et al. Prepn. of pyrazolopyrimidodiazepine derivs. as multi-targeted inhibitors of Aurora A/B and KDR for the treatment of cancer. Faming Zhuanli Shenqing. CN 109020980 A 20181218. 2018.
   Google Scholar
• Zhang J, Lu W, Pan X, et al. Pyrazole-triazole compounds as antiangiogenic drugs and their preparation, pharmaceutical compositions and use in the treatment of angiogenic diseases. Faming Zhuanli Shenqing. CN 108689999 A 20181023. 2018.
   Google Scholar
• Zhang J, Lu W, Wang S, et al. Process of preparation of optical affinity probe molecule based on VEGFR-2 inhibitor B14. Faming Zhuanli Shenqing. CN 109503553 A 20190322. 2019.
   Google Scholar
• Zhou Y, Xu T, Wang Z, et al. Preparation of antitumor drug with multiple kinase inhibitory activities. Faming Zhuanli Shenqing. CN 108440404 A 20180824. 2018.
   Google Scholar
• Hu Y, Geng M, Ren W, et al. Preparation of the o-aminoheteroaryl alkynyl-containing compound and their application as anticancer agents. Faming Zhuanli Shenqing. CN 108456163 A 20180828. 2018.
   Google Scholar
• Liu J, Chen Y, Liu Y, et al. Pyridazinone-4-phenoxypyridine compounds as VEGFR2 inhibitors and their preparation, pharmaceutical compositions and use in the treatment of cancer. Faming Zhuanli Shenqing. CN 109096250 A 20181228. 2018.
   Google Scholar
• Li J, Huang D, Zhang Q, et al. Substituted arylamino-arylheterocyclic compound and application as antitumor drug. Faming Zhuanli Shenqing. CN 107793363 A 20180313. 2018.
   Google Scholar
• Moehler M, Maderer A, Dannhardt G, et al. Preparation of 3-(5-fluoroindolyl)-4-arylmaleimide compounds and their use in tumor treatment. PCT Int. Appl. WO 2017114863 A1 20170706. 2017.
   Google Scholar
• Moehler M, Maderer A, Dannhardt G, et al. Preparation of 3-(5-fluoroindolyl)-4-arylmaleimide compounds and their use in tumor treatment. Eur. Pat. Appl. EP 3187495 A1 20170705. 2017.
   Google Scholar
• Meng F, Guoqing L, Xinyang L, et al. Preparing method and application of 2-indolone-triazole antitumor compound. Faming Zhuanli Shenqing. CN 111153889 A 20200515. 2020.
   Google Scholar
• Jin F, Feng Y, Wang Y, et al. Heterocyclic compounds as multi-target kinase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of complex heterogeneous diseases. Faming Zhuanli Shenqing. CN 108530464 A 20180914. 2018.
   Google Scholar
• Jing F, Feng Y, Wang Y, et al. Heterocyclic compounds as multi-target kinase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of complex heterogeneous diseases. PCT Int. Appl. WO 2018157737 A1 20180907. 2018.
   Google Scholar
• Liu J, Liu Q, Liu X, et al. Indazole kinase inhibitor and application. PCT Int. Appl. WO 2020087565 A1 20200507. 2020.
   Google Scholar
• Hu C, Sun S, Zhang C, et al. 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea compound, its preparation and application. Faming Zhuanli Shenqing. CN 110003176 A 20190712. 2019.
   Google Scholar
• Li J, Lu Y, Mao F, et al. Preparation of substituted [(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]urea compounds useful as receptor tyrosine kinase inhibitors for the treatment of cancer. Faming Zhuanli Shenqing. CN 108117551 A 20180605. 2018.
   Google Scholar
• Zheng P, Zhu W, Tu Y, et al. Preparation of quinazoline compounds containing acylhydrazone structure useful for the treatment of proliferative disease and cancer. Faming Zhuanli Shenqing. CN 106892907 A 20170627. 2017.
   Google Scholar
• Cho EH, Shin HJ, Ki MH, et al. Pyridine derivative for inhibiting Raf kinase and vascular endothelial growth factor receptor, and method for the preparation thereof. PCT Int. Appl. WO 2017135589 A1 20170810. 2017.
   Google Scholar
• Yang S, Wei Y. Preparation of 3-acetylenyl-pyrazole-pyrimidine derivatives as tyrosine kinase inhibitors useful in the treatment of cancer. U.S. Pat. Appl. Publ. US 20170305920 A1 20171026. 2017.
   Google Scholar
• Wu X, Wang Y, Fu Y, et al. Preparation of the 1H-pyrazolo[3,4-d]pyrimidine compound and their application as the anticancer agents. Faming Zhuanli Shenqing. CN 107383014 A 20171124. 2017.
   Google Scholar
• Zhang Q, Liu Y, Hu C. Dioxoquinazoline and dioxoquinoline compounds as tyrosine kinase inhibitors and preparations thereof. Faming Zhuanli Shenqing. CN 110862397 A 20200306. 2020.
   Google Scholar
• Zhang Q, Yu S, Sun Y, et al. Urea-substituted aromatic ring-linked dioxane and quinazoline or quinoline compound, composition and application thereof. PCT Int. Appl. WO 2020042972 A1 20200305. 2020.
   Google Scholar
• Zhang Q, Zhang H, Yang L, et al. Dioxanoquinazoline, dioxanoquinazoline-type compound, preparation method and application. PCT Int. Appl. WO 2018153293 A1 20180830. 2018.
   Google Scholar
• Liu J, Liu Q, Liu X, et al. Preparation of carbazole derivatives as kinase inhibitors. PCT Int. Appl. WO 2019119481 A1 20190627. 2019.
   Google Scholar
• Liu J, Liu Q, Liu X, et al. .Preparation of carbazole derivatives as kinase inhibitors Faming Zhuanli Shenqing. CN 109942544 A 20190628. 2019.
   Google Scholar
• Li J, Huang D, Wang W, et al. Preparation of pyrazole derivatives as antitumor drugs. Faming Zhuanli Shenqing. CN 107286140 A 20171024. 2017.
   Google Scholar
• Hu Y, Geng M, Ren W, et al. Preparation of the o-aminoheteroaryl alkynyl-containing compound and their application as anticancer agents. PCT Int. Appl. WO 2018149382 A1 2018082. 2018.
   Google Scholar
• Liu J, Liu Q, Liu X, et al. Indazole kinase inhibitor and application. Faming Zhuanli Shenqing. CN 111138426 A 20200512. 2020.
   Google Scholar
• Liu JO, Li Y, Pasunooti KK, et al. Preparation of Itraconazole analogs and use thereof. U.S. Pat. Appl. Publ. US 20190040046 A1 20190207. 2019.
   Google Scholar
• Kulkarni VM, Modi SJ. 1,5-Disubstituted naphthalenes as anticancer agents. Indian Pat. Appl. IN 201921012102 A 20200807. 2020.
   Google Scholar
• Erickson C, Rusconi CP, Levy M, et al. Compositions including pan-variant-specific aptamers binding to and inhibiting VEGF-A and their use in prevention and/or treatment of ocular disorders. PCT Int. Appl. WO 2020146731 A1 20200716. 2020.
   Google Scholar
• Mashima T, Wakatsuki T, Seimiya H, et al. Novel treatment method using a combination of VEGFR2 antibody and anti-VEGF antibody for controlling angiogenesis in tumor cells. From PCT Int. Appl. WO 2020138486 A1 20200702. 2020.
   Google Scholar
• Wu X, Xu C, Wang Z, et al. Long-acting and low-toxic recombinant anti-VEGF humanized monoclonal antibody for cancer immunotherapy. Faming Zhuanli Shenqing. CN 110003328 A 20190712. 2019.
   Google Scholar
• Wu X, Xu C, Wang Z, et al. Long-acting and low-toxic recombinant anti-VEGF humanized monoclonal antibody for cancer immunotherapy. PCT Int. Appl. WO 2019134686 A1 20190711. 2019.
   Google Scholar
• Zhou H, Gu X, Bai Y. Preparation of monoclonal anti-human VEGFR2 antibodies for diagnosis and treatment of neovascularization-induced diseases. PCT Int. Appl. WO 2018161798 A1 20180913. 2018.
   Google Scholar
• Li T, Liu J, Wu C. Preparation of bispecific anti-human VEGFR2 and CD16A antibody for inhibition of tumor growth and metastasis. Faming Zhuanli Shenqing. CN 108409861 A 20180817. 2018.
   Google Scholar
• Chao H, Wong WY, Tian B, et al. Preparation of anti-VEGFR-2 single domain antibodies, conjugates and fusion proteins for cancer diagnosis and therapy. PCT Int. Appl. WO 2018126316 A1 20180712. 2018.
   Google Scholar
• Zhu Z, Lu D. Bispecific antibodies binding to human PD-L1 and human KDR. PCT Int. Appl. WO 2017136562 A2 20170810. 2017.
   Google Scholar
• Lai J-S, Ai L-S, Lai Y-D, et al. Anti-VEGFR2 antibodies and uses thereof in therapy and diagnosis. PCT Int. Appl. WO 2017117384 A1 20170706. 2017.
   Google Scholar
• Gastwirt R, Zhou H, Gray JD, et al. Fully human antibodies that bind to vascular endothelial growth factor receptor 2. U.S. Pat. Appl. Publ. US 20170166644 A1 20170615. 2017.
   Google Scholar
• Qi H, Wang X, Yan X, et al. Chimeric fusion protein XCL1-VEGFR2 for targeting VEGFR2 and inducing CD8+ T cells to prevent and treat metastasis. Faming Zhuanli Shenqing. CN 111440244 A 20200724. 2020.
   Google Scholar
• Mashima T, Wakatsuki T, Seimiya H, et al. Novel treatment method using a combination of VEGFR2 antibody and anti-VEGF antibody for controlling angiogenesis in tumor cells. PCT Int. Appl. WO 2020138486 A1 20200702. 2020.
   Google Scholar
• Guo Z, Shen B, Wu L. Human monoclonal anti-vascular endothelial growth factor receptor 2 single-chain antibody for cancer immunotherapy. PCT Int. Appl. WO 2020042653 A1 20200305. 2020.
   Google Scholar
• Shaik F, Cuthbert GA, Homer-Vanniasinkam S, et al. Structural basis for vascular endothelial growth factor receptor activation and implications for disease therapy. Biomolecules. 2020;10(12):1673.
   Web of Science ®Google Scholar
• Yan L, Hsu K, Beckman RA. Antibody-based therapy for solid tumors. Cancer J. 2008 May-Jun;14(3):178–183.
   PubMed Web of Science ®Google Scholar
• Hwang K, Yoon JH, Lee JH, et al. Recent advances in monoclonal antibody therapy for colorectal cancers. Biomedicines. 2021;9(1):39.
   PubMed Web of Science ®Google Scholar
• Kazazi-Hyseni F, Beijnen JH, Schellens JH. Bevacizumab. Oncologist. 2010;15(8):819–825.
   PubMed Web of Science ®Google Scholar
• Zhaoying F, Xiang J. Aptamers, the nucleic acid antibodies, in cancer therapy. Int J Mol Sci. 2020 Apr;21(8):2793.
   Web of Science ®Google Scholar
• Han J, Gao L, Wang J, et al. Application and development of aptamer in cancer: from clinical diagnosis to cancer therapy. J Cancer. 2020;11(23):6902–6915.
   PubMed Web of Science ®Google Scholar
• Hartmann JT, Haap M, Kopp HG, et al. Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects. Curr Drug Metab. 2009 Jun;10(5):470–481.
   PubMed Web of Science ®Google Scholar
• Fujita KI, Ishida H, Kubota Y, et al. Toxicities of receptor tyrosine kinase inhibitors in cancer pharmacotherapy: management with clinical pharmacology. Curr Drug Metab. 2017;18(3):186–198.
   PubMed Web of Science ®Google Scholar
• Itatani Y, Kawada K, Yamamoto T, et al. Resistance to anti-angiogenic therapy in cancer-alterations to anti-VEGF pathway. Int J Mol Sci. 2018 Apr 18;19(4):1232.
   PubMed Web of Science ®Google Scholar
• Zirlik K, Duyster J. Anti-angiogenics: current situation and future perspectives. Oncol Res Treat. 2018;41(4):166–171.
   PubMed Web of Science ®Google Scholar
• Liu M, Guo F. Recent updates on cancer immunotherapy. Precis Clin Med. 2018;1(2):65–74.
   PubMedGoogle Scholar
• Esfahani K, Roudaia L, Buhlaiga N, et al. A review of cancer immunotherapy: from the past, to the present, to the future. Curr Oncol. 2020;27(Suppl 12):S87–S97.
   PubMedGoogle Scholar
• Li T, Kang G, Wang T, et al. Tumor angiogenesis and anti-angiogenic gene therapy for cancer. Oncol Lett. 2018 Jul;16(1):687–702.
   PubMed Web of Science ®Google Scholar
• Jain KK. Personalized immuno-oncology. Med Princ Pract. 2020 Aug 25. DOI:https://doi.org/10.1159/000511107.
   Google Scholar
• Zhang P, Zhai Y, Cai Y, et al. Nanomedicine-based immunotherapy for the treatment of cancer metastasis. Adv Mater. 2019 Dec;31(49):e1904156.
   PubMed Web of Science ®Google Scholar
• Li YJ, Wu JY, Wang JM, et al. Emerging nanomedicine-based strategies for preventing metastasis of pancreatic cancer. J Control Release. 2020 Apr 10;320: 105–111.
   PubMed Web of Science ®Google Scholar
• Martin JD, Cabral H, Stylianopoulos T, et al. Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges. Nat Rev Clin Oncol. 2020 Apr;17(4):251–266.
   PubMed Web of Science ®Google Scholar
• Baetke SC, Lammers T, Kiessling F. Applications of nanoparticles for diagnosis and therapy of cancer. Br J Radiol. 2015 Oct;88(1054):20150207.
   PubMed Web of Science ®Google Scholar