Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Topics in Medicinal Chemistry
  4. Fast Track Articles
  5. Fast Track Article
image of Targeting c-Met in Cancer Therapy: Unravelling Structure-Activity Relationships and Docking Insights for Enhanced Anticancer Drug Design

Abstract

The c-Met receptor, a pivotal player in oncogenesis and tumor progression, has become a compelling target for anticancer drug development. This review explores the intricate landscape of Structure-Activity Relationship [SAR] studies and molecular binding analyses performed on c-Met inhibitors. Through a comprehensive examination of various chemical scaffolds and modifications, SAR investigations have elucidated critical molecular features essential for the potent inhibition of c-Met activity. Additionally, molecular docking studies have provided invaluable insights into how c-Met inhibitors interact with their target receptor, facilitating the rational design of novel compounds with enhanced efficacy and selectivity. This review highlights key findings from recent SAR and docking studies, particularly focusing on the structural determinants that govern inhibition potency and selectivity. Furthermore, the integration of computational methodologies with experimental approaches has accelerated the discovery and optimization of c-Met inhibitors, fostering the advancement of promising candidates for clinical applications. Overall, this review underscores the pivotal role of SAR and molecular docking studies in advancing our understanding of c-Met inhibition and guiding the rational design of next-generation anticancer agents targeting this pathway.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266331025241015084546
2024-10-31
2024-12-26

  • From This Site

    /content/journals/ctmc/10.2174/0115680266331025241015084546
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Crepaldi T. Gallo S. Comoglio P.M. The MET oncogene: Thirty years of insights into molecular mechanisms driving malignancy. Pharmaceuticals (Basel) 2024 17 4 448 10.3390/ph17040448 38675409
    [Google Scholar]
  2. Salarinejad S. Seyfi S. Hayashi S. Moghimi S. Toolabi M. Taslimi P. Firoozpour L. Usui T. Foroumadi A. Design, synthesis, and biological evaluation of new biaryl derivatives of cycloalkyl diacetamide bearing chalcone moiety as type II c-MET kinase inhibitors. Mol. Divers. 2024 ••• 1 14 10.1007/s11030‑024‑10807‑x 38466553
    [Google Scholar]
  3. Barzaman K. Vafaei R. Samadi M. Kazemi M.H. Hosseinzadeh A. Merikhian P. Moradi-Kalbolandi S. Eisavand M.R. Dinvari H. Farahmand L. Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk. Cancer Cell Int. 2022 22 1 259 10.1186/s12935‑022‑02658‑z 35986321
    [Google Scholar]
  4. Underiner T.L. Herbertz T. Miknyoczki S.J. Discovery of small molecule c-Met inhibitors: Evolution and profiles of clinical candidates. Anticancer Agents Med. Chem. 2010 10 1 7 27 10.2174/1871520611009010007 20015007
    [Google Scholar]
  5. Wang Q. Li Y. Yuan H. Peng L. Dai Z. Sun Y. Liu R. Li W. Li J. Zhu C. Hypoxia preconditioning of human amniotic mesenchymal stem cells enhances proliferation and migration and promotes their homing via the HGF/C-MET signaling axis to augment the repair of acute liver failure. Tissue Cell 2024 87 102326 10.1016/j.tice.2024.102326 38442547
    [Google Scholar]
  6. Yao S. Liu X. Feng Y. Li Y. Xiao X. Han Y. Xia S. Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment. Int. J. Mol. Sci. 2024 25 16 9101 10.3390/ijms25169101 39201787
    [Google Scholar]
  7. Wang H. Rao B. Lou J. Li J. Liu Z. Li A. Cui G. Ren Z. Yu Z. The function of the HGF/c-Met axis in hepatocellular carcinoma. Front. Cell Dev. Biol. 2020 8 55 10.3389/fcell.2020.00055 32117981
    [Google Scholar]
  8. Mohan C.D. Shanmugam M.K. Gowda S.G.S. Chinnathambi A. Rangappa K.S. Sethi G. c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy. Phytomedicine 2024 128 155379 10.1016/j.phymed.2024.155379 38503157
    [Google Scholar]
  9. Nandi B. Del Valle J.P. Samur M.K. Gibbons A.J. Prabhala R.H. Munshi N.C. Gold J.S. CCL20 induces colorectal cancer neoplastic epithelial cell proliferation, migration, and further CCL20 production through autocrine HGF-c-Met and MSP-MSPR signaling pathways. Oncotarget 2021 12 24 2323 2337 10.18632/oncotarget.28131 34853656
    [Google Scholar]
  10. Jabbarzadeh Kaboli P. Chen H.F. Babaeizad A. Roustai Geraylow K. Yamaguchi H. Hung M.C. Unlocking c-MET: A comprehensive journey into targeted therapies for breast cancer. Cancer Lett. 2024 588 216780 10.1016/j.canlet.2024.216780 38462033
    [Google Scholar]
  11. Jin F. Lin Y. Yuan W. Wu S. Yang M. Ding S. Liu J. Chen Y. Recent advances in c-Met-based dual inhibitors in the treatment of cancers. Eur. J. Med. Chem. 2024 272 116477 10.1016/j.ejmech.2024.116477 38733884
    [Google Scholar]
  12. Al-Ghabkari A. Huang B. Park M. Aberrant MET receptor tyrosine kinase signaling in glioblastoma: targeted therapy and future directions. Cells 2024 13 3 218 10.3390/cells13030218 38334610
    [Google Scholar]
  13. Kumar V. Yochum Z.A. Devadassan P. Huang E.H.B. Miller E. Baruwal R. Rumde P.H. GaitherDavis A.L. Stabile L.P. Burns T.F. TWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer. Oncogene 2024 43 19 1431 1444 10.1038/s41388‑024‑02987‑5 38485737
    [Google Scholar]
  14. Mer A.H. Mirzaei Y. Misamogooe F. Bagheri N. Bazyari A. Keshtkaran Z. Meyfour A. Shahedi A. Amirkhani Z. Jafari A. Barpour N. Jahandideh S. Rezaei B. Nikmanesh Y. Abdollahpour-Alitappeh M. Progress of antibody–drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies. Drug Deliv. Transl. Res. 2024 ••• 1 26 10.1007/s13346‑024‑01564‑3 38597995
    [Google Scholar]
  15. Liu S. Dai W. Jin B. Jiang F. Huang H. Hou W. Lan J. Jin Y. Peng W. Pan J. Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets. Mol. Cancer 2024 23 1 122 10.1186/s12943‑024‑02033‑8 38844984
    [Google Scholar]
  16. Raj S. Role of c-MET in metabolic dysregulations in head and neck cancer. Doctor of Philosophy, School of Health Science and Technology, UPES
    [Google Scholar]
  17. Ding C. Qiu Y. Zhang J. Wei W. Gao H. Yuan Y. Wang X. Clinicopathological characteristics of Non-Small Cell Lung Cancer (NSCLC) patients with c-MET exon 14 skipping mutation, MET overexpression and amplification. BMC Pulm. Med. 2023 23 1 240 10.1186/s12890‑023‑02482‑9 37400762
    [Google Scholar]
  18. Remon J. Hendriks L.E.L. Mountzios G. García-Campelo R. Saw S.P.L. Uprety D. Recondo G. Villacampa G. Reck M. MET alterations in NSCLC—current perspectives and future challenges. J. Thorac. Oncol. 2023 18 4 419 435 10.1016/j.jtho.2022.10.015 36441095
    [Google Scholar]
  19. Van Herpe F. Van Cutsem E. The Role of cMET in Gastric Cancer—A Review of the Literature. Cancers (Basel) 2023 15 7 1976 10.3390/cancers15071976 37046637
    [Google Scholar]
  20. Röcken C. Predictive biomarkers in gastric cancer. J. Cancer Res. Clin. Oncol. 2023 149 1 467 481 10.1007/s00432‑022‑04408‑0 36260159
    [Google Scholar]
  21. Al Bitar S. El-Sabban M. Doughan S. Abou-Kheir W. Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond. World J. Gastroenterol. 2023 29 9 1395 1426 10.3748/wjg.v29.i9.1395 36998426
    [Google Scholar]
  22. Okano S. Yamashiro Y. Onagi H. Sasa K. Hayashi T. Takahashi M. Sugimoto K. Sakamoto K. Yao T. Saito T. Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics. Histopathology 2023 83 5 733 742 10.1111/his.15015 37503542
    [Google Scholar]
  23. Kumar H. Gupta N.V. Jain R. Madhunapantula S.V. Babu C.S. Kesharwani S.S. Dey S. Jain V. A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer. J. Adv. Res. 2023 54 271 292 10.1016/j.jare.2023.02.005 36791960
    [Google Scholar]
  24. Jaradat S.K. Ayoub N.M. Al Sharie A.H. Aldaod J.M. Targeting receptor tyrosine kinases as a novel strategy for the treatment of triple-negative breast cancer. Technol. Cancer Res. Treat. 2024 23 15330338241234780 10.1177/15330338241234780 38389413
    [Google Scholar]
  25. Musa S. Amara N. Selawi A. Wang J. Marchini C. Agbarya A. Mahajna J. Overcoming Chemoresistance in Cancer: The Promise of Crizotinib. Cancers (Basel) 2024 16 13 2479 10.3390/cancers16132479 39001541
    [Google Scholar]
  26. Lee Y.Y. Ryu J.Y. Cho Y.J. Choi J.Y. Choi J.J. Choi C.H. Sa J.K. Hwang J.R. Lee J.W. The anti-tumor effects of AZD4547 on ovarian cancer cells: differential responses based on c-Met and FGF19/FGFR4 expression. Cancer Cell Int. 2024 24 1 43 10.1186/s12935‑024‑03235‑2 38273381
    [Google Scholar]
  27. Choi H.Y. Chang J.E. Targeted therapy for cancers: from ongoing clinical trials to FDA-approved drugs. Int. J. Mol. Sci. 2023 24 17 13618 10.3390/ijms241713618 37686423
    [Google Scholar]
  28. Albadari N. Xie Y. Li W. Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling. Front. Pharmacol. 2024 14 1340401 10.3389/fphar.2023.1340401 38269272
    [Google Scholar]
  29. Rivas S. Marín A. Samtani S. González-Feliú E. Armisén R. MET signaling pathways, resistance mechanisms, and opportunities for target therapies. Int. J. Mol. Sci. 2022 23 22 13898 10.3390/ijms232213898 36430388
    [Google Scholar]
  30. Fu J. Su X. Li Z. Deng L. Liu X. Feng X. Peng J. HGF/c-MET pathway in cancer: from molecular characterization to clinical evidence. Oncogene 2021 40 28 4625 4651 10.1038/s41388‑021‑01863‑w 34145400
    [Google Scholar]
  31. Wood G.E. Hockings H. Hilton D.M. Kermorgant S. The role of MET in chemotherapy resistance. Oncogene 2021 40 11 1927 1941 10.1038/s41388‑020‑01577‑5 33526881
    [Google Scholar]
  32. Guo R. Luo J. Chang J. Rekhtman N. Arcila M. Drilon A. MET-dependent solid tumours — molecular diagnosis and targeted therapy. Nat. Rev. Clin. Oncol. 2020 17 9 569 587 10.1038/s41571‑020‑0377‑z 32514147
    [Google Scholar]
  33. Faiella A. Riccardi F. Cartenì G. Chiurazzi M. Onofrio L. The emerging role of c‐met in carcinogenesis and clinical implications as a possible therapeutic target. J. Oncol. 2022 2022 1 1 12 10.1155/2022/5179182 35069735
    [Google Scholar]
  34. Christensen J.G. Burrows J. Salgia R. c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett. 2005 225 1 1 26 10.1016/j.canlet.2004.09.044 15922853
    [Google Scholar]
  35. Xiong H. Cheng J. Zhang J. Zhang Q. Xiao Z. Zhang H. Tang Q. Zheng P. Design, synthesis, and biological evaluation of pyridineamide derivatives containing a 1, 2, 3-triazole fragment as type II c-Met Inhibitors. Molecules 2019 25 1 10 10.3390/molecules25010010 31861448
    [Google Scholar]
  36. Tang S. Sun C. He X. Gan W. Wang L. Qiao D. Guan X. Xu S. Zheng P. Zhu W. Design, synthesis, and biological evaluation of 4-(2-fluorophenoxy)-7-methoxyquinazoline derivatives as dual EGFR/c-Met inhibitors for the treatment of NSCLC. Eur. J. Med. Chem. 2024 263 115939 10.1016/j.ejmech.2023.115939 37984296
    [Google Scholar]
  37. Puccini A. Marín-Ramos N.I. Bergamo F. Schirripa M. Lonardi S. Lenz H.J. Loupakis F. Battaglin F. Safety and tolerability of c-MET inhibitors in cancer. Drug Saf. 2019 42 2 211 233 10.1007/s40264‑018‑0780‑x 30649748
    [Google Scholar]
  38. Ashrafizadeh M. Dai J. Torabian P. Nabavi N. Aref A.R. Aljabali A.A.A. Tambuwala M. Zhu M. Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance. Cell. Mol. Life Sci. 2024 81 1 214 10.1007/s00018‑024‑05236‑w 38733529
    [Google Scholar]
  39. Hsu R. Benjamin D.J. Nagasaka M. The Development and Role of Capmatinib in the Treatment of MET-Dysregulated Non-Small Cell Lung Cancer—A Narrative Review. Cancers (Basel) 2023 15 14 3561 10.3390/cancers15143561 37509224
    [Google Scholar]
  40. Liam C.K. Ahmad A.R. Hsia T.C. Zhou J. Kim D.W. Soo R.A. Cheng Y. Lu S. Shin S.W. Yang J.C.H. Zhang Y. Zhao J. Berghoff K. Bruns R. Johne A. Wu Y.L. Randomized trial of tepotinib plus gefitinib versus chemotherapy in EGFR-mutant NSCLC with EGFR inhibitor resistance due to MET amplification: INSIGHT final analysis. Clin. Cancer Res. 2023 29 10 1879 1886 10.1158/1078‑0432.CCR‑22‑3318 36971777
    [Google Scholar]
  41. Wang C. Lu X. Targeting MET: discovery of small molecule inhibitors as non-small cell lung cancer therapy. J. Med. Chem. 2023 66 12 7670 7697 10.1021/acs.jmedchem.3c00028 37262349
    [Google Scholar]
  42. Paik P.K. Felip E. Veillon R. Sakai H. Cortot A.B. Garassino M.C. Mazieres J. Viteri S. Senellart H. Van Meerbeeck J. Raskin J. Reinmuth N. Conte P. Kowalski D. Cho B.C. Patel J.D. Horn L. Griesinger F. Han J.Y. Kim Y.C. Chang G.C. Tsai C.L. Yang J.C.H. Chen Y.M. Smit E.F. van der Wekken A.J. Kato T. Juraeva D. Stroh C. Bruns R. Straub J. Johne A. Scheele J. Heymach J.V. Le X. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N. Engl. J. Med. 2020 383 10 931 943 10.1056/NEJMoa2004407 32469185
    [Google Scholar]
  43. Ayoub N.M. Ibrahim D.R. Alkhalifa A.E. Al-Husein B.A. Crizotinib induced antitumor activity and synergized with chemotherapy and hormonal drugs in breast cancer cells via downregulating MET and estrogen receptor levels. Invest. New Drugs 2021 39 1 77 88 10.1007/s10637‑020‑00989‑0 32833135
    [Google Scholar]
  44. Sun Y. Wu Y. Zheng Y. Role of Tepotinib, Capmatinib and Crizotinib in non-small cell lung cancer. Highlights in Science. Engineering and Technology. 2022 6 321 327
    [Google Scholar]
  45. Santoni M. Iacovelli R. Colonna V. Klinz S. Mauri G. Nuti M. Antitumor effects of the multi-target tyrosine kinase inhibitor cabozantinib: a comprehensive review of the preclinical evidence. Expert Rev. Anticancer Ther. 2021 21 9 1029 1054 10.1080/14737140.2021.1919090 34445927
    [Google Scholar]
  46. Sachkova A.A. Andreeva D.V. Tikhomirov A.S. Scherbakov A.M. Salnikova D.I. Sorokin D.V. Bogdanov F.B. Rysina Y.D. Shchekotikhin A.E. Shchegravina E.S. Fedorov A.Y. Design, synthesis and in vitro investigation of cabozantinib-based PROTACs to target c-Met kinase. Pharmaceutics 2022 14 12 2829 10.3390/pharmaceutics14122829 36559322
    [Google Scholar]
  47. Huang X. Li E. Shen H. Wang X. Tang T. Zhang X. Xu J. Tang Z. Guo C. Bai X. Liang T. Targeting the HGF/MET axis in cancer therapy: challenges in resistance and opportunities for improvement. Front. Cell Dev. Biol. 2020 8 152 10.3389/fcell.2020.00152 32435640
    [Google Scholar]
  48. Zhan H. Tu S. Zhang F. Shao A. Lin J. MicroRNAs and long non-coding RNAs in c-Met-regulated cancers. Front. Cell Dev. Biol. 2020 8 145 10.3389/fcell.2020.00145 32219093
    [Google Scholar]
  49. Ayoub N.M. Ibrahim D.R. Alkhalifa A.E. Overcoming resistance to targeted therapy using MET inhibitors in solid cancers: evidence from preclinical and clinical studies. Med. Oncol. 2021 38 12 143 10.1007/s12032‑021‑01596‑6 34665336
    [Google Scholar]
  50. Moosavi F. Giovannetti E. Peters G.J. Firuzi O. Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer. Crit. Rev. Oncol. Hematol. 2021 160 103234 10.1016/j.critrevonc.2021.103234 33497758
    [Google Scholar]
  51. Hong L. Zhang J. Heymach J.V. Le X. Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer. Ther. Adv. Med. Oncol. 2021 13 10.1177/1758835921992976 33643443
    [Google Scholar]
  52. Dai J. Ashrafizadeh M. Aref A.R. Sethi G. Ertas Y.N. Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy. Drug Discov. Today 2024 29 7 103981 10.1016/j.drudis.2024.103981 38614161
    [Google Scholar]
  53. Lai G.G.Y. Guo R. Drilon A. Shao Weng Tan D. Refining patient selection of MET-activated non-small cell lung cancer through biomarker precision. Cancer Treat. Rev. 2022 110 102444 10.1016/j.ctrv.2022.102444 36108503
    [Google Scholar]
  54. Oliveres H. Pineda E. Maurel J. MET inhibitors in cancer: pitfalls and challenges. Expert Opin. Investig. Drugs 2020 29 1 73 85 10.1080/13543784.2020.1699532 31783719
    [Google Scholar]
  55. Goltsov A.A. Fang B. Pandita T.K. Maru D.M. Swisher S.G. Hofstetter W.L. HER2 confers resistance to foretinib inhibition of MET-amplified esophageal adenocarcinoma cells. Ann. Thorac. Surg. 2018 105 2 363 370 10.1016/j.athoracsur.2017.09.003 29223420
    [Google Scholar]
  56. Doi T. Results of Phase 1 Studies of Golvatinib (E7050), A c-Met and EPH Receptor-Targeted Multi-Kinase Inhibitor. Ann. Oncol. 2012 23 xi26 10.1016/S0923‑7534(20)31988‑8
    [Google Scholar]
  57. Semrad T.J. Kim E.J. Tanaka M.S. Sands J. Roberts C. Burich R.A. Li Y. Gandara D.R. Lara P. Jr Mack P.C. Phase II study of dovitinib in patients progressing on anti-vascular endothelial growth factor therapy. Cancer Treat. Res. Commun. 2017 10 21 26 10.1016/j.ctarc.2016.12.002 28736761
    [Google Scholar]
  58. Molina A.M. Hutson T.E. Nosov D. Tomczak P. Lipatov O. Sternberg C.N. Motzer R. Eisen T. Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study. Eur. J. Cancer 2018 94 87 94 10.1016/j.ejca.2018.02.009 29547835
    [Google Scholar]
  59. Fargnoli J. Henley B.J. Wautlet B.S. Borzilleri R. 106 Preclinical studies and characterization of BMS-794833, a small molecule inhibitor of Met and VEGFR-2 kinases. Eur. J. Cancer, Suppl. 2010 8 7 41 10.1016/S1359‑6349(10)71811‑5
    [Google Scholar]
  60. Zhang W. Ai J. Shi D. Peng X. Ji Y. Liu J. Geng M. Li Y. Discovery of novel type II c-Met inhibitors based on BMS-777607. Eur. J. Med. Chem. 2014 80 254 266 10.1016/j.ejmech.2014.04.056 24792774
    [Google Scholar]
  61. Wang Q. Quan H. Zhao J. Xie C. Wang L. Lou L. RON confers lapatinib resistance in HER2-positive breast cancer cells. Cancer Lett. 2013 340 1 43 50 10.1016/j.canlet.2013.06.022 23811285
    [Google Scholar]
  62. Jani J.P. Finn R.S. Campbell M. Coleman K.G. Connell R.D. Currier N. Emerson E.O. Floyd E. Harriman S. Kath J.C. Morris J. Moyer J.D. Pustilnik L.R. Rafidi K. Ralston S. Rossi A.M.K. Steyn S.J. Wagner L. Winter S.M. Bhattacharya S.K. Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor. Cancer Res. 2007 67 20 9887 9893 10.1158/0008‑5472.CAN‑06‑3559 17942920
    [Google Scholar]
  63. Cho B.C. Simi A. Sabari J. Vijayaraghavan S. Moores S. Spira A. Amivantamab, an epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) bispecific antibody, designed to enable multiple mechanisms of action and broad clinical applications. Clin. Lung Cancer 2023 24 2 89 97 10.1016/j.cllc.2022.11.004 36481319
    [Google Scholar]
  64. Eder J.P. Vande Woude G.F. Boerner S.A. LoRusso P.M. Novel therapeutic inhibitors of the c-Met signaling pathway in cancer. Clin. Cancer Res. 2009 15 7 2207 2214 10.1158/1078‑0432.CCR‑08‑1306 19318488
    [Google Scholar]
  65. Zhang H. Gan W. Fan D. Zheng P. Lv Q. Pan Q. Zhu W. Novel quinazoline-based dual EGFR/c-Met inhibitors overcoming drug resistance for the treatment of NSCLC: Design, synthesis and anti-tumor activity. Bioorg. Chem. 2024 142 106938 10.1016/j.bioorg.2023.106938 37913585
    [Google Scholar]
  66. Nan X. Li H.J. Fang S.B. Li Q.Y. Wu Y.C. Structure-based discovery of novel 4-(2-fluorophenoxy)quinoline derivatives as c-Met inhibitors using isocyanide-involved multicomponent reactions. Eur. J. Med. Chem. 2020 193 112241 10.1016/j.ejmech.2020.112241 32200199
    [Google Scholar]
  67. Huang D. Chen Y. Yang J. Zhao B. Wang S. Chai T. Cui J. Zhou X. Shang Z. Design, Synthesis, and Biological Evaluation of 2-Substituted Aniline Pyrimidine Derivatives as Potent Dual Mer/c-Met Inhibitors. Molecules 2024 29 2 475 10.3390/molecules29020475 38257391
    [Google Scholar]
  68. Raj S. Kesari K.K. Kumar A. Rathi B. Sharma A. Gupta P.K. Jha S.K. Jha N.K. Slama P. Roychoudhury S. Kumar D. Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer. Mol. Cancer 2022 21 1 31 10.1186/s12943‑022‑01503‑1 35081970
    [Google Scholar]
  69. Alamshany Z.M. Algamdi E.M. Othman I.M.M. Anwar M.M. Nossier E.S. New pyrazolopyridine and pyrazolothiazole-based compounds as anti-proliferative agents targeting c-Met kinase inhibition: design, synthesis, biological evaluation, and computational studies. RSC Advances 2023 13 19 12889 12905 10.1039/D3RA01931D 37114032
    [Google Scholar]
  70. Xiong H. Zhang J. Zhang Q. Duan Y. Zhang H. Zheng P. Tang Q. Design, synthesis and biological evaluation of 4-(pyridin-4-yloxy)benzamide derivatives bearing a 5-methylpyridazin-3(2H)-one fragment. Bioorg. Med. Chem. Lett. 2020 30 9 127076 10.1016/j.bmcl.2020.127076 32173195
    [Google Scholar]
  71. Feng Y. Ren Y.L. Zhao L.M. Xue G.Q. Yu W.H. Yang J.Q. Liu J-W. Design, synthesis and biological evaluation of novel α‐acyloxycarboxamide‐based derivatives as c‐met inhibitors. Chin. J. Chem. 2021 39 8 2241 2250 10.1002/cjoc.202100106
    [Google Scholar]
  72. Mortazavi M. Divar M. Damghani T. Moosavi F. Saso L. Pirhadi S. Khoshneviszadeh M. Edraki N. Firuzi O. Study of the anticancer effect of new quinazolinone hydrazine derivatives as receptor tyrosine kinase inhibitors. Front Chem. 2022 10 969559 10.3389/fchem.2022.969559 36465863
    [Google Scholar]
  73. Li J. Gu W. Bi X. Li H. Liao C. Liu C. Huang W. Qian H. Design, synthesis, and biological evaluation of thieno[2,3-d]pyrimidine derivatives as novel dual c-Met and VEGFR-2 kinase inhibitors. Bioorg. Med. Chem. 2017 25 24 6674 6679 10.1016/j.bmc.2017.11.010 29146452
    [Google Scholar]
  74. Nigam V. Singh S. Kasana S. Kumar S. Das Kurmi B. Das Gupta G. Patel P. Revolutionizing indole synthesis: A microwave-powered approach. ChemistrySelect 2024 9 23 e202402171 10.1002/slct.202402171
    [Google Scholar]
  75. Wang L.X. Liu X. Xu S. Tang Q. Duan Y. Xiao Z. Zhi J. Jiang L. Zheng P. Zhu W. Discovery of novel pyrrolo-pyridine/pyrimidine derivatives bearing pyridazinone moiety as c-Met kinase inhibitors. Eur. J. Med. Chem. 2017 141 538 551 10.1016/j.ejmech.2017.10.027 29107421
    [Google Scholar]
  76. Wang L. Xu S. Chen X. Liu X. Duan Y. Kong D. Zhao D. Zheng P. Tang Q. Zhu W. Synthesis and bioevaluation study of novel N -methylpicolinamide and thienopyrimidine derivatives as selectivity c-Met kinase inhibitors. Bioorg. Med. Chem. 2018 26 1 245 256 10.1016/j.bmc.2017.11.039 29203143
    [Google Scholar]
  77. Luo G. Ma Y. Liang X. Xie G. Luo Y. Zha D. Wang S. Yu L. Zheng X. Wu W. Zhang C. Design, synthesis and antitumor evaluation of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives as potential c-Met inhibitors. Bioorg. Chem. 2020 104 104356 10.1016/j.bioorg.2020.104356 33142417
    [Google Scholar]
  78. Zhang Q. Liu X. Gan W. Wu J. Zhou H. Yang Z. Zhang Y. Liao M. Yuan P. Xu S. Zheng P. Zhu W. Discovery of triazolo-pyridazine/-pyrimidine derivatives bearing aromatic (heterocycle)-coupled azole units as class II c-Met inhibitors. ACS Omega 2020 5 27 16482 16490 10.1021/acsomega.0c00838 32685812
    [Google Scholar]
  79. Huang D. Yang J. Zhang Q. Wang G. Zhang Z. Zhang Y. Li J. Structure-guided design and development of novel N-phenylpyrimidin-2-amine derivatives as potential c-Met inhibitors. Eur. J. Med. Chem. 2021 223 113648 10.1016/j.ejmech.2021.113648 34175535
    [Google Scholar]
  80. Nan X. Zhang J. Li H.J. Wu R. Fang S.B. Zhang Z.Z. Wu Y.C. Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction. Eur. J. Med. Chem. 2020 200 112470 10.1016/j.ejmech.2020.112470 32505087
    [Google Scholar]
  81. Ibrahim H.A. Awadallah F.M. Refaat H.M. Amin K.M. Design, synthesis and molecular modeling study for some new 2-substituted benzimidazoles as dual inhibitors for VEGFR-2 and c-Met. Future Med. Chem. 2018 10 5 493 509 10.4155/fmc‑2017‑0174 29431476
    [Google Scholar]
  82. Ibrahim H.S. Albakri M.E. Mahmoud W.R. Allam H.A. Reda A.M. Abdel-Aziz H.A. Synthesis and biological evaluation of some novel thiobenzimidazole derivatives as anti-renal cancer agents through inhibition of c-MET kinase. Bioorg. Chem. 2019 85 337 348 10.1016/j.bioorg.2019.01.006 30658233
    [Google Scholar]
  83. Zhang B. Liu X. Xiong H. Zhang Q. Sun X. Yang Z. Xu S. Zheng P. Zhu W. Discovery of [1,2,4]triazolo[4,3- a ]pyrazine derivatives bearing a 4-oxo-pyridazinone moiety as potential c-Met kinase inhibitors. New J. Chem. 2020 44 21 9053 9063 10.1039/D0NJ00575D
    [Google Scholar]
  84. Liu X. Li Y. Zhang Q. Pan Q. Zheng P. Dai X. Bai Z. Zhu W. Design, Synthesis, and Biological Evaluation of [1,2,4]triazolo[4,3-a] Pyrazine Derivatives as Novel Dual c-Met/VEGFR-2 Inhibitors. Front Chem. 2022 10 815534 10.3389/fchem.2022.815534 35464202
    [Google Scholar]
  85. Liu J. Yang D. Yang X. Nie M. Wu G. Wang Z. Li W. Liu Y. Gong P. Design, synthesis and biological evaluation of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety as c-Met kinase inhibitors. Bioorg. Med. Chem. 2017 25 16 4475 4486 10.1016/j.bmc.2017.06.037 28716639
    [Google Scholar]
  86. Lien V.T. Pettersen S. Haugen M.H. Olberg D.E. Mælandsmo G.M. Klaveness J. Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors. Arch. Pharm. (Weinheim) 2019 352 9 1900101 10.1002/ardp.201900101 31414521
    [Google Scholar]
  87. Nan X. Jiang Y.F. Li H.J. Wang J.H. Wu Y.C. Design, synthesis and evaluation of sulfonylurea-containing 4-phenoxyquinolines as highly selective c-Met kinase inhibitors. Bioorg. Med. Chem. 2019 27 13 2801 2812 10.1016/j.bmc.2019.05.007 31079967
    [Google Scholar]
  88. Yang Y. Li Y. Hou Y. Qin M. Gong P. Liu J. Zhao Y. Design, synthesis, and biological evaluation of 4-phenoxyquinoline derivatives as potent c-Met kinase inhibitor. Bioorg. Med. Chem. Lett. 2019 29 23 126666 10.1016/j.bmcl.2019.126666 31629631
    [Google Scholar]
  89. Wang Z. Shi J. Zhu X. Zhao W. Gong Y. Hao X. Hou Y. Liu Y. Ding S. Liu J. Chen Y. Design, synthesis and biological evaluation of novel 4-phenoxypyridine based 3-oxo-3,4-dihydroquinoxaline-2-carboxamide derivatives as potential c-Met kinase inhibitors. Bioorg. Chem. 2020 105 104371 10.1016/j.bioorg.2020.104371 33075664
    [Google Scholar]
  90. Zhang L. Zhao J. Zhang B. Lu T. Chen Y. Discovery of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as novel, potent and selective c-Met kinase inhibitors: Synthesis, SAR study, and biological activity. Eur. J. Med. Chem. 2018 150 809 816 10.1016/j.ejmech.2018.03.049 29602036
    [Google Scholar]
  91. Nan X. Wang Q.X. Xing S.J. Liang Z.G. Design, synthesis, and biological evaluation of thiazole/thiadiazole carboxamide scaffold-based derivatives as potential c-Met kinase inhibitors for cancer treatment. J. Enzyme Inhib. Med. Chem. 2023 38 1 2247183 10.1080/14756366.2023.2247183 37642355
    [Google Scholar]
  92. Wang M.S. Zhuo L.S. Yang F.P. Wang W.J. Huang W. Yang G.F. Synthesis and biological evaluation of new MET inhibitors with 1,6-naphthyridinone scaffold. Eur. J. Med. Chem. 2020 185 111803 10.1016/j.ejmech.2019.111803 31677447
    [Google Scholar]
  93. Ahmed E.M. Khalil N.A. Taher A.T. Refaey R.H. Nissan Y.M. Triazolopyridazine derivatives: Synthesis, cytotoxic evaluation, c-Met kinase activity and molecular docking. Bioorg. Chem. 2019 92 103272 10.1016/j.bioorg.2019.103272 31539742
    [Google Scholar]
  94. Gu W. Dai Y. Qiang H. Shi W. Liao C. Zhao F. Huang W. Qian H. Discovery of novel 2-substituted-4-(2-fluorophenoxy) pyridine derivatives possessing pyrazolone and triazole moieties as dual c-Met/VEGFR-2 receptor tyrosine kinase inhibitors. Bioorg. Chem. 2017 72 116 122 10.1016/j.bioorg.2017.04.001 28411406
    [Google Scholar]
  95. Kasana S. Nigam V. Singh S. Kurmi B.D. Patel P. A New Insight Into The Huisgen Reaction: Heterogeneous Copper Catalyzed Azide‐Alkyne Cycloaddition for the Synthesis of 1,4‐Disubstituted Triazole (From 2018–2023). Chem. Biodivers. 2024 21 6 e202400109 10.1002/cbdv.202400109 38640439
    [Google Scholar]
  96. Tang Q. Duan Y. Wang L. Wang M. Ouyang Y. Wang C. Mei H. Tang S. Xiong Y. Zheng P. Gong P. Zhu W. Synthesis and antiproliferative activity of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety. Eur. J. Med. Chem. 2018 143 266 275 10.1016/j.ejmech.2017.11.034 29197731
    [Google Scholar]
  97. Wang W. Xu S. Duan Y. Liu X. Li X. Wang C. Zhao B. Zheng P. Zhu W. Synthesis and bioevaluation and doking study of 1 H -pyrrolo[2,3- b ]pyridine derivatives bearing aromatic hydrazone moiety as c-Met inhibitors. Eur. J. Med. Chem. 2018 145 315 327 10.1016/j.ejmech.2017.12.078 29331754
    [Google Scholar]
  98. El-Wakil M.H. Ashour H.M. Saudi M.N. Hassan A.M. Labouta I.M. Design, synthesis and molecular modeling studies of new series of antitumor 1,2,4-triazines with potential c-Met kinase inhibitory activity. Bioorg. Chem. 2018 76 154 165 10.1016/j.bioorg.2017.11.006 29175587
    [Google Scholar]
  99. Wei D. Fan H. Zheng K. Qin X. Yang L. Yang Y. Duan Y. Zhang Q. Zeng C. Hu L. Synthesis and anti-tumor activity of [1,4] dioxino [2,3-f] quinazoline derivatives as dual inhibitors of c-Met and VEGFR-2. Bioorg. Chem. 2019 88 102916 10.1016/j.bioorg.2019.04.010 31026719
    [Google Scholar]
  100. Wang M. Xu S. Lei H. Wang C. Xiao Z. Jia S. Zhi J. Zheng P. Zhu W. Design, synthesis and antitumor activity of Novel Sorafenib derivatives bearing pyrazole scaffold. Bioorg. Med. Chem. 2017 25 20 5754 5763 10.1016/j.bmc.2017.09.003 28927801
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266331025241015084546
Loading
Targeting c-Met in Cancer Therapy: Unravelling Structure-Activity Relationships and Docking Insights for Enhanced Anticancer Drug Design
Bentham Science Publishers ; https://doi.org/10.2174/0115680266331025241015084546
/content/journals/ctmc/10.2174/0115680266331025241015084546
/content/journals/ctmc/10.2174/0115680266331025241015084546
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: c-Met overexpression ; SAR ; Anticancer agents ; Molecular docking ; c-Met inhibitors

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test