Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Topics in Medicinal Chemistry
  4. Volume 25, Issue 4
  5. Article
Volume 25, Issue 4
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266331025241015084546
2024-10-31
2025-05-08

  • 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. CrepaldiT. GalloS. ComoglioP.M. The MET oncogene: Thirty years of insights into molecular mechanisms driving malignancy.Pharmaceuticals (Basel)202417444810.3390/ph17040448 38675409
     [Google Scholar]
  2. SalarinejadS. SeyfiS. HayashiS. MoghimiS. ToolabiM. TaslimiP. FiroozpourL. UsuiT. ForoumadiA. Design, synthesis, and biological evaluation of new biaryl derivatives of cycloalkyl diacetamide bearing chalcone moiety as type II c-MET kinase inhibitors.Mol. Divers.202411410.1007/s11030‑024‑10807‑x 38466553
     [Google Scholar]
  3. BarzamanK. VafaeiR. SamadiM. KazemiM.H. HosseinzadehA. MerikhianP. Moradi-KalbolandiS. EisavandM.R. DinvariH. FarahmandL. Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk.Cancer Cell Int.202222125910.1186/s12935‑022‑02658‑z 35986321
     [Google Scholar]
  4. UnderinerT.L. HerbertzT. MiknyoczkiS.J. Discovery of small molecule c-Met inhibitors: Evolution and profiles of clinical candidates.Anticancer. Agents Med. Chem.201010172710.2174/1871520611009010007 20015007
     [Google Scholar]
  5. WangQ. LiY. YuanH. PengL. DaiZ. SunY. LiuR. LiW. LiJ. ZhuC. 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 Cell20248710232610.1016/j.tice.2024.102326 38442547
     [Google Scholar]
  6. YaoS. LiuX. FengY. LiY. XiaoX. HanY. XiaS. Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.Int. J. Mol. Sci.20242516910110.3390/ijms25169101 39201787
     [Google Scholar]
  7. WangH. RaoB. LouJ. LiJ. LiuZ. LiA. CuiG. RenZ. YuZ. The function of the HGF/c-Met axis in hepatocellular carcinoma.Front. Cell Dev. Biol.202085510.3389/fcell.2020.00055 32117981
     [Google Scholar]
  8. MohanC.D. ShanmugamM.K. GowdaS.G.S. ChinnathambiA. RangappaK.S. SethiG. c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy.Phytomedicine202412815537910.1016/j.phymed.2024.155379 38503157
     [Google Scholar]
  9. NandiB. Del ValleJ.P. SamurM.K. GibbonsA.J. PrabhalaR.H. MunshiN.C. GoldJ.S. CCL20 induces colorectal cancer neoplastic epithelial cell proliferation, migration, and further CCL20 production through autocrine HGF-c-Met and MSP-MSPR signaling pathways.Oncotarget202112242323233710.18632/oncotarget.28131 34853656
     [Google Scholar]
  10. Jabbarzadeh KaboliP. ChenH.F. BabaeizadA. Roustai GeraylowK. YamaguchiH. HungM.C. Unlocking c-MET: A comprehensive journey into targeted therapies for breast cancer.Cancer Lett.202458821678010.1016/j.canlet.2024.216780 38462033
     [Google Scholar]
  11. JinF. LinY. YuanW. WuS. YangM. DingS. LiuJ. ChenY. Recent advances in c-Met-based dual inhibitors in the treatment of cancers.Eur. J. Med. Chem.202427211647710.1016/j.ejmech.2024.116477 38733884
     [Google Scholar]
  12. Al-GhabkariA. HuangB. ParkM. Aberrant MET receptor tyrosine kinase signaling in glioblastoma: targeted therapy and future directions.Cells202413321810.3390/cells13030218 38334610
     [Google Scholar]
  13. KumarV. YochumZ.A. DevadassanP. HuangE.H.B. MillerE. BaruwalR. RumdeP.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.Oncogene202443191431144410.1038/s41388‑024‑02987‑5 38485737
     [Google Scholar]
  14. MerA.H. MirzaeiY. MisamogooeF. BagheriN. BazyariA. KeshtkaranZ. MeyfourA. ShahediA. AmirkhaniZ. JafariA. BarpourN. JahandidehS. RezaeiB. NikmaneshY. Abdollahpour-AlitappehM. Progress of antibody–drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies. Drug Deliv. Transl. Res.,202412610.1007/s13346‑024‑01564‑338597995
     [Google Scholar]
  15. LiuS. DaiW. JinB. JiangF. HuangH. HouW. LanJ. JinY. PengW. PanJ. Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.Mol. Cancer202423112210.1186/s12943‑024‑02033‑8 38844984
     [Google Scholar]
  16. RajS. 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. DingC. QiuY. ZhangJ. WeiW. GaoH. YuanY. WangX. Clinicopathological characteristics of Non-Small Cell Lung Cancer (NSCLC) patients with c-MET exon 14 skipping mutation, MET overexpression and amplification.BMC Pulm. Med.202323124010.1186/s12890‑023‑02482‑9 37400762
     [Google Scholar]
  18. RemonJ. HendriksL.E.L. MountziosG. García-CampeloR. SawS.P.L. UpretyD. RecondoG. VillacampaG. ReckM. MEt alterations in NSCLC—current perspectives and future challenges.J. Thorac. Oncol.202318441943510.1016/j.jtho.2022.10.015 36441095
     [Google Scholar]
  19. Van HerpeF. Van CutsemE. The Role of cMET in Gastric Cancer—A Review of the Literature.Cancers (Basel)2023157197610.3390/cancers15071976 37046637
     [Google Scholar]
  20. RöckenC. Predictive biomarkers in gastric cancer.J. Cancer Res. Clin. Oncol.2023149146748110.1007/s00432‑022‑04408‑0 36260159
     [Google Scholar]
  21. Al BitarS. El-SabbanM. DoughanS. Abou-KheirW. Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World J. Gastroenterol.20232991395142610.3748/wjg.v29.i9.1395 36998426
     [Google Scholar]
  22. OkanoS. YamashiroY. OnagiH. SasaK. HayashiT. TakahashiM. SugimotoK. SakamotoK. YaoT. SaitoT. Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics.Histopathology202383573374210.1111/his.15015 37503542
     [Google Scholar]
  23. KumarH. GuptaN.V. JainR. MadhunapantulaS.V. BabuC.S. KesharwaniS.S. DeyS. JainV. A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.J. Adv. Res.20235427129210.1016/j.jare.2023.02.005 36791960
     [Google Scholar]
  24. JaradatS.K. AyoubN.M. Al SharieA.H. AldaodJ.M. Targeting receptor tyrosine kinases as a novel strategy for the treatment of triple-negative breast cancer.Technol. Cancer Res. Treat.2024231533033824123478010.1177/15330338241234780 38389413
     [Google Scholar]
  25. MusaS. AmaraN. SelawiA. WangJ. MarchiniC. AgbaryaA. MahajnaJ. Overcoming Chemoresistance in Cancer: The Promise of Crizotinib.Cancers (Basel)20241613247910.3390/cancers16132479 39001541
     [Google Scholar]
  26. LeeY.Y. RyuJ.Y. ChoY.J. ChoiJ.Y. ChoiJ.J. ChoiC.H. SaJ.K. HwangJ.R. LeeJ.W. The anti-tumor effects of AZD4547 on ovarian cancer cells: differential responses based on c-Met and FGF19/FGFR4 expression.Cancer Cell Int.20242414310.1186/s12935‑024‑03235‑2 38273381
     [Google Scholar]
  27. ChoiH.Y. ChangJ.E. Targeted therapy for cancers: from ongoing clinical trials to FDA-approved drugs.Int. J. Mol. Sci.202324171361810.3390/ijms241713618 37686423
     [Google Scholar]
  28. AlbadariN. XieY. LiW. Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.Front. Pharmacol.202414134040110.3389/fphar.2023.1340401 38269272
     [Google Scholar]
  29. RivasS. MarínA. SamtaniS. González-FeliúE. ArmisénR. MET signaling pathways, resistance mechanisms, and opportunities for target therapies.Int. J. Mol. Sci.202223221389810.3390/ijms232213898 36430388
     [Google Scholar]
  30. FuJ. SuX. LiZ. DengL. LiuX. FengX. PengJ. HGF/c-MET pathway in cancer: from molecular characterization to clinical evidence.Oncogene202140284625465110.1038/s41388‑021‑01863‑w 34145400
     [Google Scholar]
  31. WoodG.E. HockingsH. HiltonD.M. KermorgantS. The role of MET in chemotherapy resistance.Oncogene202140111927194110.1038/s41388‑020‑01577‑5 33526881
     [Google Scholar]
  32. GuoR. LuoJ. ChangJ. RekhtmanN. ArcilaM. DrilonA. MET-dependent solid tumours — molecular diagnosis and targeted therapy.Nat. Rev. Clin. Oncol.202017956958710.1038/s41571‑020‑0377‑z 32514147
     [Google Scholar]
  33. FaiellaA. RiccardiF. CartenìG. ChiurazziM. OnofrioL. The emerging role of c‐met in carcinogenesis and clinical implications as a possible therapeutic target.J. Oncol.20222022111210.1155/2022/5179182 35069735
     [Google Scholar]
  34. ChristensenJ.G. BurrowsJ. SalgiaR. c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention.Cancer Lett.2005225112610.1016/j.canlet.2004.09.044 15922853
     [Google Scholar]
  35. XiongH. ChengJ. ZhangJ. ZhangQ. XiaoZ. ZhangH. TangQ. ZhengP. Design, synthesis, and biological evaluation of pyridineamide derivatives containing a 1, 2, 3-triazole fragment as type II c-Met Inhibitors.Molecules20192511010.3390/molecules25010010 31861448
     [Google Scholar]
  36. TangS. SunC. HeX. GanW. WangL. QiaoD. GuanX. XuS. ZhengP. ZhuW. 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.202426311593910.1016/j.ejmech.2023.115939 37984296
     [Google Scholar]
  37. PucciniA. Marín-RamosN.I. BergamoF. SchirripaM. LonardiS. LenzH.J. LoupakisF. BattaglinF. Safety and tolerability of c-MET inhibitors in cancer.Drug Saf.201942221123310.1007/s40264‑018‑0780‑x 30649748
     [Google Scholar]
  38. AshrafizadehM. DaiJ. TorabianP. NabaviN. ArefA.R. AljabaliA.A.A. TambuwalaM. ZhuM. Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance.Cell. Mol. Life Sci.202481121410.1007/s00018‑024‑05236‑w 38733529
     [Google Scholar]
  39. HsuR. BenjaminD.J. NagasakaM. The Development and Role of Capmatinib in the Treatment of MET-Dysregulated Non-Small Cell Lung Cancer—A Narrative Review.Cancers (Basel)20231514356110.3390/cancers15143561 37509224
     [Google Scholar]
  40. LiamC.K. AhmadA.R. HsiaT.C. ZhouJ. KimD.W. SooR.A. ChengY. LuS. ShinS.W. YangJ.C.H. ZhangY. ZhaoJ. BerghoffK. BrunsR. JohneA. WuY.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.202329101879188610.1158/1078‑0432.CCR‑22‑3318 36971777
     [Google Scholar]
  41. WangC. LuX. Targeting MET: discovery of small molecule inhibitors as non-small cell lung cancer therapy.J. Med. Chem.202366127670769710.1021/acs.jmedchem.3c00028 37262349
     [Google Scholar]
  42. PaikP.K. FelipE. VeillonR. SakaiH. CortotA.B. GarassinoM.C. MazieresJ. ViteriS. SenellartH. Van MeerbeeckJ. RaskinJ. ReinmuthN. ConteP. KowalskiD. ChoB.C. PatelJ.D. HornL. GriesingerF. HanJ.Y. KimY.C. ChangG.C. TsaiC.L. YangJ.C.H. ChenY.M. SmitE.F. van der WekkenA.J. KatoT. JuraevaD. StrohC. BrunsR. StraubJ. JohneA. ScheeleJ. HeymachJ.V. LeX. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations.N. Engl. J. Med.20203831093194310.1056/NEJMoa2004407 32469185
     [Google Scholar]
  43. AyoubN.M. IbrahimD.R. AlkhalifaA.E. Al-HuseinB.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 Drugs2021391778810.1007/s10637‑020‑00989‑0 32833135
     [Google Scholar]
  44. SunY. WuY. ZhengY. Role of Tepotinib, Capmatinib and Crizotinib in non-small cell lung cancer. Highlights in Science.Engineering and Technology.20226321327
     [Google Scholar]
  45. SantoniM. IacovelliR. ColonnaV. KlinzS. MauriG. NutiM. Antitumor effects of the multi-target tyrosine kinase inhibitor cabozantinib: a comprehensive review of the preclinical evidence.Expert Rev. Anticancer Ther.20212191029105410.1080/14737140.2021.1919090 34445927
     [Google Scholar]
  46. SachkovaA.A. AndreevaD.V. TikhomirovA.S. ScherbakovA.M. SalnikovaD.I. SorokinD.V. BogdanovF.B. RysinaY.D. ShchekotikhinA.E. ShchegravinaE.S. FedorovA.Y. Design, synthesis and in vitro investigation of cabozantinib-based PROTACs to target c-Met kinase.Pharmaceutics20221412282910.3390/pharmaceutics14122829 36559322
     [Google Scholar]
  47. HuangX. LiE. ShenH. WangX. TangT. ZhangX. XuJ. TangZ. GuoC. BaiX. LiangT. Targeting the HGF/MET axis in cancer therapy: challenges in resistance and opportunities for improvement.Front. Cell Dev. Biol.2020815210.3389/fcell.2020.00152 32435640
     [Google Scholar]
  48. ZhanH. TuS. ZhangF. ShaoA. LinJ. MicroRNAs and long non-coding RNAs in c-Met-regulated cancers.Front. Cell Dev. Biol.2020814510.3389/fcell.2020.00145 32219093
     [Google Scholar]
  49. AyoubN.M. IbrahimD.R. AlkhalifaA.E. Overcoming resistance to targeted therapy using MET inhibitors in solid cancers: evidence from preclinical and clinical studies.Med. Oncol.2021381214310.1007/s12032‑021‑01596‑6 34665336
     [Google Scholar]
  50. MoosaviF. GiovannettiE. PetersG.J. FiruziO. Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer.Crit. Rev. Oncol. Hematol.202116010323410.1016/j.critrevonc.2021.103234 33497758
     [Google Scholar]
  51. HongL. ZhangJ. HeymachJ.V. LeX. Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer.Ther. Adv. Med. Oncol.20211310.1177/1758835921992976 33643443
     [Google Scholar]
  52. DaiJ. AshrafizadehM. ArefA.R. SethiG. ErtasY.N. Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy.Drug Discov. Today202429710398110.1016/j.drudis.2024.103981 38614161
     [Google Scholar]
  53. LaiG.G.Y. GuoR. DrilonA. ShaoWeng Tan D. Refining patient selection of MET-activated non-small cell lung cancer through biomarker precision.Cancer Treat. Rev.202211010244410.1016/j.ctrv.2022.102444 36108503
     [Google Scholar]
  54. OliveresH. PinedaE. MaurelJ. MET inhibitors in cancer: pitfalls and challenges.Expert Opin. Investig. Drugs2020291738510.1080/13543784.2020.1699532 31783719
     [Google Scholar]
  55. GoltsovA.A. FangB. PanditaT.K. MaruD.M. SwisherS.G. HofstetterW.L. HER2 confers resistance to foretinib inhibition of MET-amplified esophageal adenocarcinoma cells.Ann. Thorac. Surg.2018105236337010.1016/j.athoracsur.2017.09.003 29223420
     [Google Scholar]
  56. DoiT. Results of Phase 1 Studies of Golvatinib (E7050), A c-Met and EPH Receptor-Targeted Multi-Kinase Inhibitor.Ann. Oncol.201223xi2610.1016/S0923‑7534(20)31988‑8
     [Google Scholar]
  57. SemradT.J. KimE.J. TanakaM.S. SandsJ. RobertsC. BurichR.A. LiY. GandaraD.R. LaraP.Jr MackP.C. Phase II study of dovitinib in patients progressing on anti-vascular endothelial growth factor therapy.Cancer Treat. Res. Commun.201710212610.1016/j.ctarc.2016.12.002 28736761
     [Google Scholar]
  58. MolinaA.M. HutsonT.E. NosovD. TomczakP. LipatovO. SternbergC.N. MotzerR. EisenT. Efficacy of tivozanib treatment after sorafenib in patients with advanced renal cell carcinoma: crossover of a phase 3 study.Eur. J. Cancer201894879410.1016/j.ejca.2018.02.009 29547835
     [Google Scholar]
  59. FargnoliJ. HenleyB.J. WautletB.S. BorzilleriR. 106 Preclinical studies and characterization of BMS-794833, a small molecule inhibitor of Met and VEGFR-2 kinases.Eur. J. Cancer, Suppl.2010874110.1016/S1359‑6349(10)71811‑5
     [Google Scholar]
  60. ZhangW. AiJ. ShiD. PengX. JiY. LiuJ. GengM. LiY. Discovery of novel type II c-Met inhibitors based on BMS-777607.Eur. J. Med. Chem.20148025426610.1016/j.ejmech.2014.04.056 24792774
     [Google Scholar]
  61. WangQ. QuanH. ZhaoJ. XieC. WangL. LouL. RON confers lapatinib resistance in HER2-positive breast cancer cells.Cancer Lett.20133401435010.1016/j.canlet.2013.06.022 23811285
     [Google Scholar]
  62. JaniJ.P. FinnR.S. CampbellM. ColemanK.G. ConnellR.D. CurrierN. EmersonE.O. FloydE. HarrimanS. KathJ.C. MorrisJ. MoyerJ.D. PustilnikL.R. RafidiK. RalstonS. RossiA.M.K. SteynS.J. WagnerL. WinterS.M. BhattacharyaS.K. Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor.Cancer Res.200767209887989310.1158/0008‑5472.CAN‑06‑3559 17942920
     [Google Scholar]
  63. ChoB.C. SimiA. SabariJ. VijayaraghavanS. MooresS. SpiraA. 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 Cancer2023242899710.1016/j.cllc.2022.11.004 36481319
     [Google Scholar]
  64. EderJ.P. Vande WoudeG.F. BoernerS.A. LoRussoP.M. Novel therapeutic inhibitors of the c-Met signaling pathway in cancer.Clin. Cancer Res.20091572207221410.1158/1078‑0432.CCR‑08‑1306 19318488
     [Google Scholar]
  65. ZhangH. GanW. FanD. ZhengP. LvQ. PanQ. ZhuW. Novel quinazoline-based dual EGFR/c-Met inhibitors overcoming drug resistance for the treatment of NSCLC: Design, synthesis and anti-tumor activity.Bioorg. Chem.202414210693810.1016/j.bioorg.2023.106938 37913585
     [Google Scholar]
  66. NanX. LiH.J. FangS.B. LiQ.Y. WuY.C. Structure-based discovery of novel 4-(2-fluorophenoxy)quinoline derivatives as c-Met inhibitors using isocyanide-involved multicomponent reactions.Eur. J. Med. Chem.202019311224110.1016/j.ejmech.2020.112241 32200199
     [Google Scholar]
  67. HuangD. ChenY. YangJ. ZhaoB. WangS. ChaiT. CuiJ. ZhouX. ShangZ. Design, Synthesis, and Biological Evaluation of 2-Substituted Aniline Pyrimidine Derivatives as Potent Dual Mer/c-Met Inhibitors.Molecules202429247510.3390/molecules29020475 38257391
     [Google Scholar]
  68. RajS. KesariK.K. KumarA. RathiB. SharmaA. GuptaP.K. JhaS.K. JhaN.K. SlamaP. RoychoudhuryS. KumarD. Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer.Mol. Cancer20222113110.1186/s12943‑022‑01503‑1 35081970
     [Google Scholar]
  69. AlamshanyZ.M. AlgamdiE.M. OthmanI.M.M. AnwarM.M. NossierE.S. New pyrazolopyridine and pyrazolothiazole-based compounds as anti-proliferative agents targeting c-Met kinase inhibition: design, synthesis, biological evaluation, and computational studies.RSC Advances20231319128891290510.1039/D3RA01931D 37114032
     [Google Scholar]
  70. XiongH. ZhangJ. ZhangQ. DuanY. ZhangH. ZhengP. TangQ. Design, synthesis and biological evaluation of 4-(pyridin-4-yloxy)benzamide derivatives bearing a 5-methylpyridazin-3(2H)-one fragment.Bioorg. Med. Chem. Lett.202030912707610.1016/j.bmcl.2020.127076 32173195
     [Google Scholar]
  71. FengY. RenY.L. ZhaoL.M. XueG.Q. YuW.H. YangJ.Q. LiuJ-W. Design, synthesis and biological evaluation of novel α‐acyloxycarboxamide‐based derivatives as c‐met inhibitors.Chin. J. Chem.20213982241225010.1002/cjoc.202100106
     [Google Scholar]
  72. MortazaviM. DivarM. DamghaniT. MoosaviF. SasoL. PirhadiS. KhoshneviszadehM. EdrakiN. FiruziO. Study of the anticancer effect of new quinazolinone hydrazine derivatives as receptor tyrosine kinase inhibitors.Front Chem.20221096955910.3389/fchem.2022.969559 36465863
     [Google Scholar]
  73. LiJ. GuW. BiX. LiH. LiaoC. LiuC. HuangW. QianH. 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.201725246674667910.1016/j.bmc.2017.11.010 29146452
     [Google Scholar]
  74. NigamV. SinghS. KasanaS. KumarS. Das KurmiB. Das GuptaG. PatelP. Revolutionizing indole synthesis: A microwave-powered approach.ChemistrySelect2024923e20240217110.1002/slct.202402171
     [Google Scholar]
  75. WangL.X. LiuX. XuS. TangQ. DuanY. XiaoZ. ZhiJ. JiangL. ZhengP. ZhuW. Discovery of novel pyrrolo-pyridine/pyrimidine derivatives bearing pyridazinone moiety as c-Met kinase inhibitors.Eur. J. Med. Chem.201714153855110.1016/j.ejmech.2017.10.027 29107421
     [Google Scholar]
  76. WangL. XuS. ChenX. LiuX. DuanY. KongD. ZhaoD. ZhengP. TangQ. ZhuW. Synthesis and bioevaluation study of novel N -methylpicolinamide and thienopyrimidine derivatives as selectivity c-Met kinase inhibitors.Bioorg. Med. Chem.201826124525610.1016/j.bmc.2017.11.039 29203143
     [Google Scholar]
  77. LuoG. MaY. LiangX. XieG. LuoY. ZhaD. WangS. YuL. ZhengX. WuW. ZhangC. Design, synthesis and antitumor evaluation of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives as potential c-Met inhibitors.Bioorg. Chem.202010410435610.1016/j.bioorg.2020.104356 33142417
     [Google Scholar]
  78. ZhangQ. LiuX. GanW. WuJ. ZhouH. YangZ. ZhangY. LiaoM. YuanP. XuS. ZhengP. ZhuW. Discovery of triazolo-pyridazine/-pyrimidine derivatives bearing aromatic (heterocycle)-coupled azole units as class II c-Met inhibitors.ACS Omega2020527164821649010.1021/acsomega.0c00838 32685812
     [Google Scholar]
  79. HuangD. YangJ. ZhangQ. WangG. ZhangZ. ZhangY. LiJ. Structure-guided design and development of novel N-phenylpyrimidin-2-amine derivatives as potential c-Met inhibitors.Eur. J. Med. Chem.202122311364810.1016/j.ejmech.2021.113648 34175535
     [Google Scholar]
  80. NanX. ZhangJ. LiH.J. WuR. FangS.B. ZhangZ.Z. WuY.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.202020011247010.1016/j.ejmech.2020.112470 32505087
     [Google Scholar]
  81. IbrahimH.A. AwadallahF.M. RefaatH.M. AminK.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.201810549350910.4155/fmc‑2017‑0174 29431476
     [Google Scholar]
  82. IbrahimH.S. AlbakriM.E. MahmoudW.R. AllamH.A. RedaA.M. Abdel-AzizH.A. Synthesis and biological evaluation of some novel thiobenzimidazole derivatives as anti-renal cancer agents through inhibition of c-MET kinase.Bioorg. Chem.20198533734810.1016/j.bioorg.2019.01.006 30658233
     [Google Scholar]
  83. ZhangB. LiuX. XiongH. ZhangQ. SunX. YangZ. XuS. ZhengP. ZhuW. 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.202044219053906310.1039/D0NJ00575D
     [Google Scholar]
  84. LiuX. LiY. ZhangQ. PanQ. ZhengP. DaiX. BaiZ. ZhuW. 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.20221081553410.3389/fchem.2022.815534 35464202
     [Google Scholar]
  85. LiuJ. YangD. YangX. NieM. WuG. WangZ. LiW. LiuY. GongP. 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.201725164475448610.1016/j.bmc.2017.06.037 28716639
     [Google Scholar]
  86. LienV.T. PettersenS. HaugenM.H. OlbergD.E. MælandsmoG.M. KlavenessJ. Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors.Arch. Pharm. (Weinheim)20193529190010110.1002/ardp.201900101 31414521
     [Google Scholar]
  87. NanX. JiangY.F. LiH.J. WangJ.H. WuY.C. Design, synthesis and evaluation of sulfonylurea-containing 4-phenoxyquinolines as highly selective c-Met kinase inhibitors.Bioorg. Med. Chem.201927132801281210.1016/j.bmc.2019.05.007 31079967
     [Google Scholar]
  88. YangY. LiY. HouY. QinM. GongP. LiuJ. ZhaoY. Design, synthesis, and biological evaluation of 4-phenoxyquinoline derivatives as potent c-Met kinase inhibitor.Bioorg. Med. Chem. Lett.2019292312666610.1016/j.bmcl.2019.126666 31629631
     [Google Scholar]
  89. WangZ. ShiJ. ZhuX. ZhaoW. GongY. HaoX. HouY. LiuY. DingS. LiuJ. ChenY. 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.202010510437110.1016/j.bioorg.2020.104371 33075664
     [Google Scholar]
  90. ZhangL. ZhaoJ. ZhangB. LuT. ChenY. 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.201815080981610.1016/j.ejmech.2018.03.049 29602036
     [Google Scholar]
  91. NanX. WangQ.X. XingS.J. LiangZ.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.2023381224718310.1080/14756366.2023.2247183 37642355
     [Google Scholar]
  92. WangM.S. ZhuoL.S. YangF.P. WangW.J. HuangW. YangG.F. Synthesis and biological evaluation of new MET inhibitors with 1,6-naphthyridinone scaffold.Eur. J. Med. Chem.202018511180310.1016/j.ejmech.2019.111803 31677447
     [Google Scholar]
  93. AhmedE.M. KhalilN.A. TaherA.T. RefaeyR.H. NissanY.M. Triazolopyridazine derivatives: Synthesis, cytotoxic evaluation, c-Met kinase activity and molecular docking.Bioorg. Chem.20199210327210.1016/j.bioorg.2019.103272 31539742
     [Google Scholar]
  94. GuW. DaiY. QiangH. ShiW. LiaoC. ZhaoF. HuangW. QianH. 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.20177211612210.1016/j.bioorg.2017.04.001 28411406
     [Google Scholar]
  95. KasanaS. NigamV. SinghS. KurmiB.D. PatelP. 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.2024216e20240010910.1002/cbdv.202400109 38640439
     [Google Scholar]
  96. TangQ. DuanY. WangL. WangM. OuyangY. WangC. MeiH. TangS. XiongY. ZhengP. GongP. ZhuW. Synthesis and antiproliferative activity of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety.Eur. J. Med. Chem.201814326627510.1016/j.ejmech.2017.11.034 29197731
     [Google Scholar]
  97. WangW. XuS. DuanY. LiuX. LiX. WangC. ZhaoB. ZhengP. ZhuW. 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.201814531532710.1016/j.ejmech.2017.12.078 29331754
     [Google Scholar]
  98. El-WakilM.H. AshourH.M. SaudiM.N. HassanA.M. LaboutaI.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.20187615416510.1016/j.bioorg.2017.11.006 29175587
     [Google Scholar]
  99. WeiD. FanH. ZhengK. QinX. YangL. YangY. DuanY. ZhangQ. ZengC. HuL. 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.20198810291610.1016/j.bioorg.2019.04.010 31026719
     [Google Scholar]
  100. WangM. XuS. LeiH. WangC. XiaoZ. JiaS. ZhiJ. ZhengP. ZhuW. Design, synthesis and antitumor activity of Novel Sorafenib derivatives bearing pyrazole scaffold.Bioorg. Med. Chem.201725205754576310.1016/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
Curr. Top. Med. Chem. 25, 409 (2025); 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
Keyword(s): Anticancer agents; c-Met inhibitors; c-Met overexpression; c-Met receptor; Molecular docking; SAR

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