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Volume 25, Issue 8
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

Tyrosine kinases have emerged as key stimulatory drivers in several cancer-related pathways. This is particularly evident in non-small cell lung cancer with regulating cell growth and apoptosis and so on. Tyrosine kinase inhibitors (TKI) are one breakthrough option that could improve the life quality of cancer patients.

Objective

This study aims to find more effective tyrosine kinase inhibitors.

Methods

In this study, natural products from TargetMol that may be the potential TKI for lung cancer were screened through structure-based virtual screening and experimental validation. Moreover, the binding between the hit compounds and tyrosine kinase was explored.

Results

From the study findings, Gramicidin and Tannic acid have strong interactions with the four tyrosine kinases (ALK, TRK, MET, and ABL), and this could significantly inhibit the viability of A549 cells in a concentration-dependent manner.

Conclusion

These findings indicated that Gramicidin and Tannic acid might be potential multiple TKI and are promising anticancer agents that call for further study.

© 2025 Bentham Science Publishers
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2025-01-01
2025-04-25

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References

  1. World Health OrganizationCancer2022Available from: https://www.who.int/news-room/fact-sheets/detail/cancer
    [Google Scholar]
  2. VinodS.K. HauE. Radiotherapy treatment for lung cancer: Current status and future directions.Respirology202025S2617110.1111/resp.13870 32516852
     [Google Scholar]
  3. EttingerD.S. WoodD.E. AisnerD.L. AkerleyW. BaumanJ. ChirieacL.R. D’AmicoT.A. DeCampM.M. DillingT.J. DobelbowerM. DoebeleR.C. GovindanR. GubensM.A. HennonM. HornL. KomakiR. LacknerR.P. LanutiM. LealT.A. LeischL.J. LilenbaumR. LinJ. LooB.W.Jr MartinsR. OttersonG.A. ReckampK. RielyG.J. SchildS.E. ShapiroT.A. StevensonJ. SwansonS.J. TauerK. YangS.C. GregoryK. HughesM. Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology.J. Natl. Compr. Canc. Netw.201715450453510.6004/jnccn.2017.0050 28404761
     [Google Scholar]
  4. HirschF.R. ScagliottiG.V. MulshineJ.L. KwonR. CurranW.J.Jr WuY.L. Paz-AresL. Lung cancer: Current therapies and new targeted treatments.Lancet20173891006629931110.1016/S0140‑6736(16)30958‑8 27574741
     [Google Scholar]
  5. WangM. HerbstR.S. BoshoffC. Toward personalized treatment approaches for non-small-cell lung cancer.Nat. Med.20212781345135610.1038/s41591‑021‑01450‑2 34385702
     [Google Scholar]
  6. HerbstR.S. MorgenszternD. BoshoffC. The biology and management of non-small cell lung cancer.Nature2018553768944645410.1038/nature25183 29364287
     [Google Scholar]
  7. MurugesanS. MurugesanJ. PalaniappanS. PalaniappanS. MuruganT. SiddiquiS.S. LoganathanS. Tyrosine kinase inhibitors (TKIs) in lung cancer treatment: A comprehensive analysis.Curr. Cancer Drug Targets2021211556910.2174/1568009620666201009130008 33038912
     [Google Scholar]
  8. ChaftJ.E. RimnerA. WederW. AzzoliC.G. KrisM.G. CasconeT. Evolution of systemic therapy for stages I-III non-metastatic non-small-cell lung cancer.Nat. Rev. Clin. Oncol.202118954755710.1038/s41571‑021‑00501‑4 33911215
     [Google Scholar]
  9. BoumahdiS. de SauvageF.J. The great escape: Tumour cell plasticity in resistance to targeted therapy.Nat. Rev. Drug Discov.2020191395610.1038/s41573‑019‑0044‑1 31601994
     [Google Scholar]
  10. Sharifi-RadJ. QuispeC. PatraJ.K. SinghY.D. PandaM.K. DasG. AdetunjiC.O. MichaelO.S. SytarO. PolitoL. ŽivkovićJ. Cruz-MartinsN. Klimek-SzczykutowiczM. EkiertH. ChoudharyM.I. AyatollahiS.A. TynybekovB. KobarfardF. MunteanA.C. GrozeaI. DaştanS.D. ButnariuM. SzopaA. CalinaD. Paclitaxel: Application in modern oncology and nanomedicine-based cancer therapy.Oxid. Med. Cell. Longev.20212021368770010.1155/2021/3687700 34707776
     [Google Scholar]
  11. YoneshimaY. MoritaS. AndoM. NakamuraA. IwasawaS. YoshiokaH. GotoY. TakeshitaM. HaradaT. HiranoK. OguriT. KondoM. MiuraS. HosomiY. KatoT. KuboT. KishimotoJ. YamamotoN. NakanishiY. OkamotoI. Phase 3 trial comparing nanoparticle albumin-bound paclitaxel with docetaxel for previously treated advanced NSCLC.J. Thorac. Oncol.20211691523153210.1016/j.jtho.2021.03.027 33915251
     [Google Scholar]
  12. BoothB.W. InskeepB.D. ShahH. ParkJ.P. HayE.J. BurgK.J.L. Tannic Acid preferentially targets estrogen receptor-positive breast cancer.Int. J. Breast Cancer2013201336960910.1155/2013/369609 24369505
     [Google Scholar]
  13. DarvinP. JoungY.H. KangD.Y. SpN. ByunH.J. HwangT.S. SasidharakurupH. LeeC.H. ChoK.H. ParkK.D. LeeH.K. YangY.M. Tannic acid inhibits EGFR/STAT1/3 and enhances p38/STAT1 signalling axis in breast cancer cells.J. Cell. Mol. Med.201721472073410.1111/jcmm.13015 27862996
     [Google Scholar]
  14. DavidJ.M. OwensT.A. BarweS.P. RajasekaranA.K. Gramicidin A induces metabolic dysfunction and energy depletion leading to cell death in renal cell carcinoma cells.Mol. Cancer Ther.201312112296230710.1158/1535‑7163.MCT‑13‑0445 24006494
     [Google Scholar]
  15. ChenT. WangY. YangY. YuK. CaoX. SuF. XuH. PengY. HuY. QianF. WangZ. Gramicidin inhibits human gastric cancer cell proliferation, cell cycle and induced apoptosis.Biol. Res.20195215710.1186/s40659‑019‑0264‑1 31767027
     [Google Scholar]
  16. GongX. ZouL. WangM. ZhangY. PengS. ZhongM. ZhouJ. LiX. MaX. Gramicidin inhibits cholangiocarcinoma cell growth by suppressing EGR4.Artif. Cells Nanomed. Biotechnol.2020481535910.1080/21691401.2019.1699808 31852273
     [Google Scholar]
  17. DavidJ.M. OwensT.A. IngeL.J. BremnerR.M. RajasekaranA.K. Gramicidin A blocks tumor growth and angiogenesis through inhibition of hypoxia-inducible factor in renal cell carcinoma.Mol. Cancer Ther.201413478879910.1158/1535‑7163.MCT‑13‑0891 24493697
     [Google Scholar]
  18. WenT. SongL. HuaS. Perspectives and controversies regarding the use of natural products for the treatment of lung cancer.Cancer Med.20211072396242210.1002/cam4.3660 33650320
     [Google Scholar]
  19. RoskoskiR.Jr Properties of FDA-approved small molecule protein kinase inhibitors: A 2021 update.Pharmacol. Res.202116510546310.1016/j.phrs.2021.105463 33513356
     [Google Scholar]
  20. ElancheranR. SaravananK. DivakarS. KumariS. MaruthanilaV.L. KabilanS. RamanathanM. DeviR. KotokyJ. Design, synthesis and biological evaluation of novel 1, 3- thiazolidine-2, 4-diones as anti-prostate cancer agents.Anticancer. Agents Med. Chem.2017171317561768 28403781
     [Google Scholar]
  21. HanssonT. OostenbrinkC. van GunsterenW. Molecular dynamics simulations.Curr. Opin. Struct. Biol.200212219019610.1016/S0959‑440X(02)00308‑1 11959496
     [Google Scholar]
  22. VanommeslaegheK. HatcherE. AcharyaC. KunduS. ZhongS. ShimJ. DarianE. GuvenchO. LopesP. VorobyovI. MackerellA.D. Jr CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields.J. Comput. Chem.2010314671690 19575467
     [Google Scholar]
  23. AttwoodM.M. FabbroD. SokolovA.V. KnappS. SchiöthH.B. Trends in kinase drug discovery: Targets, indications and inhibitor design.Nat. Rev. Drug Discov.2021201183986110.1038/s41573‑021‑00252‑y 34354255
     [Google Scholar]
  24. RemonJ. PignataroD. NovelloS. PassigliaF. Current treatment and future challenges in ROS1- and ALK-rearranged advanced non-small cell lung cancer.Cancer Treat. Rev.20219510217810.1016/j.ctrv.2021.102178 33743408
     [Google Scholar]
  25. GoldingB. LuuA. JonesR. Viloria-PetitA.M. The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC).Mol. Cancer20181715210.1186/s12943‑018‑0810‑4 29455675
     [Google Scholar]
  26. HojJ.P. MayroB. PendergastA.M. TAZ-AXL-ABL2 feed-forward signaling axis promotes lung adenocarcinoma brain metastasis.Cell Rep.2019291134213434.e810.1016/j.celrep.2019.11.018 31825826
     [Google Scholar]
  27. GuJ.J. HojJ. RouseC. PendergastA.M. Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells.PLoS One20201510e024142310.1371/journal.pone.0241423 33119681
     [Google Scholar]
  28. LuttmanJ.H. HojJ.P. LinK.H. LinJ. GuJ.J. RouseC. NicholsA.G. MacIverN.J. WoodK.C. PendergastA.M. ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells.Cell Rep.202137410988010.1016/j.celrep.2021.109880 34706244
     [Google Scholar]
  29. PetridouE.T. SergentanisT.N. AntonopoulosC.N. DessyprisN. MatsoukisI.L. AronisK. EfremidisA. SyrigosC. MantzorosC.S. Insulin resistance: An independent risk factor for lung cancer?Metabolism20116081100110610.1016/j.metabol.2010.12.002 21251684
     [Google Scholar]
  30. AlthubitiM. AlmaimaniR. EidS.Y. ElzubaierM. RefaatB. IdrisS. AlqurashiT.A. El-ReadiM.Z. BTK targeting suppresses inflammatory genes and ameliorates insulin resistance.Eur. Cytokine Netw.202031416817910.1684/ecn.2020.0454 33648925
     [Google Scholar]
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Screening and in vitro Biological Evaluation of Novel Multiple Tyrosine Kinases Inhibitors as Promising Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 555 (2025); https://doi.org/10.2174/1871520623666230403104816
/content/journals/acamc/10.2174/1871520623666230403104816
/content/journals/acamc/10.2174/1871520623666230403104816
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  • Article Type:     Research Article
Keyword(s): anticancer therapy; gramicidin; Molecular dynamics simulation; natural products; tyrosine kinases; virtual screening

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