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  3. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
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Volume 25, Issue 1
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

FGFR have been demonstrated to perform a crucial role in biological processes but their over-expression has been perceived as the operator component in the occurrence and progression of different types of carcinoma. Out of all the interest around cancer, FGFR inhibitors have assembled pace over the past few years. Therefore, FGFR inhibitors are one of the main fundamental tools to reverse drug resistance, tumor growth, and angiogenesis. Currently, many FGFR inhibitors are under the development stage or have been developed. Due to great demand and hotspots, different pharmacophores were approached to access structurally diverse FGFR inhibitors. Here, we have selected to present several representative examples such as Naphthyl, Pyrimidine, Pyridazine, Indole, and Quinoline derivatives that illustrate the diversity and advances of FGFR inhibitors in medicinal chemistry. This review focuses on the SAR study of FGFR inhibitors last five years which will be a great future scope that influences the medicinal chemist to work towards more achievements in this area.

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2025-01-10

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References

  1. MehraA. SharmaV. VermaA. VenugopalS. MittalA. SinghG. KaurB. Indole derived anticancer agents.ChemistrySelect2022734e20220236110.1002/slct.202202361
     [Google Scholar]
  2. LindJ. CzernilofskyF. ValletS. PodarK. Emerging protein kinase inhibitors for the treatment of multiple myeloma.Expert Opin. Emerg. Drugs201924313315210.1080/14728214.2019.164716531327278
     [Google Scholar]
  3. VenugopalS. SharmaV. MehraA. SinghI. SinghG. DNA intercalators as anticancer agents.Chem. Biol. Drug Des.2022100458059810.1111/cbdd.1411635822451
     [Google Scholar]
  4. (a PowersC.J. McLeskeyS.W. WellsteinA. Fibroblast growth factors, their receptors and signaling.Endocr. Relat. Cancer20007316519710.1677/erc.0.007016511021964
     [Google Scholar]
  5. (b XieY. SuN. YangJ. TanQ. HuangS. JinM. NiZ. ZhangB. ZhangD. LuoF. ChenH. SunX. FengJ.Q. QiH. ChenL. FGF/FGFR signaling in health and disease.Signal Transduct. Target. Ther.20205118110.1038/s41392‑020‑00222‑732879300
     [Google Scholar]
  6. (c TouatM. IleanaE. Postel-VinayS. AndréF. SoriaJ.C. Targeting FGFR signaling in cancer.Clin. Cancer Res.201521122684269410.1158/1078‑0432.CCR‑14‑232926078430
     [Google Scholar]
  7. TiongK.H. MahL.Y. LeongC.O. Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancers.Apoptosis201318121447146810.1007/s10495‑013‑0886‑723900974
     [Google Scholar]
  8. Mossahebi-MohammadiM. QuanM. ZhangJ.S. LiX. FGF signaling pathway: A key regulator of stem cell pluripotency.Front. Cell Dev. Biol.202087910.3389/fcell.2020.0007932133359
     [Google Scholar]
  9. ProcaccioL. DamuzzoV. Di SarraF. RussiA. TodinoF. DadduzioV. BergamoF. PreteA.A. LonardiS. PrenenH. PalozzoA.C. LoupakisF. Safety and tolerability of anti-angiogenic protein kinase inhibitors and vascular-disrupting agents in cancer: Focus on gastrointestinal malignancies.Drug Saf.201942215917910.1007/s40264‑018‑0776‑630649744
     [Google Scholar]
  10. BovéeJ.V.M.G. HogendoornP.C.W. Non‐ossifying fibroma: A RAS‐MAPK driven benign bone neoplasm.J. Pathol.2019248212713010.1002/path.525930809793
     [Google Scholar]
  11. TuY. QuT. ChenF. Mutant hFGF23(A12D) stimulates osteoblast differentiation through FGFR3.J. Cell. Mol. Med.20192342933294210.1111/jcmm.14201
     [Google Scholar]
  12. ChaeY.K. RanganathK. HammermanP.S. VaklavasC. MohindraN. KalyanA. MatsangouM. CostaR. CarneiroB. VillaflorV.M. CristofanilliM. GilesF.J. Inhibition of the fibroblast growth factor receptor (FGFR) pathway: The current landscape and barriers to clinical application.Oncotarget201789160521607410.18632/oncotarget.1410928030802
     [Google Scholar]
  13. EswarakumarV.P. LaxI. SchlessingerJ. Cellular signaling by fibroblast growth factor receptors.Cytokine Growth Factor Rev.200516213914910.1016/j.cytogfr.2005.01.00115863030
     [Google Scholar]
  14. TurnerN. GroseR. Fibroblast growth factor signalling: From development to cancer.Nat. Rev. Cancer201010211612910.1038/nrc278020094046
     [Google Scholar]
  15. DongQ. LiS. WangW. HanL. XiaZ. WuY. TangY. LiJ. ChengX. FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways.J. Cell. Physiol.201923411195021951010.1002/jcp.2854830953354
     [Google Scholar]
  16. GoetzR. MohammadiM. Exploring mechanisms of FGF signalling through the lens of structural biology.Nat. Rev. Mol. Cell Biol.201314316618010.1038/nrm352823403721
     [Google Scholar]
  17. DienstmannR. RodonJ. PratA. Perez-GarciaJ. AdamoB. FelipE. CortesJ. IafrateA.J. NuciforoP. TaberneroJ. Genomic aberrations in the FGFR pathway: Opportunities for targeted therapies in solid tumors.Ann. Oncol.201425355256310.1093/annonc/mdt41924265351
     [Google Scholar]
  18. HelstenT. ElkinS. ArthurE. TomsonB.N. CarterJ. KurzrockR. The FGFR landscape in cancer: Analysis of 4,853 tumors by next-generation sequencing.Clin. Cancer Res.201622125926710.1158/1078‑0432.CCR‑14‑321226373574
     [Google Scholar]
  19. TiseoM. GelsominoF. AlfieriR. CavazzoniA. BozzettiC. De GiorgiA.M. PetroniniP.G. ArdizzoniA. FGFR as potential target in the treatment of squamous non small cell lung cancer.Cancer Treat. Rev.201541652753910.1016/j.ctrv.2015.04.01125959741
     [Google Scholar]
  20. HallinanN. FinnS. CuffeS. RafeeS. O’ByrneK. GatelyK. Targeting the fibroblast growth factor receptor family in cancer.Cancer Treat. Rev.201646516210.1016/j.ctrv.2016.03.01527109926
     [Google Scholar]
  21. GauglhoferC. PaurJ. SchrottmaierW.C. WingelhoferB. HuberD. NaegelenI. PirkerC. MohrT. HeinzleC. HolzmannK. MarianB. Schulte-HermannR. BergerW. KrupitzaG. GruschM. Grasl-KrauppB. Fibroblast growth factor receptor 4: A putative key driver for the aggressive phenotype of hepatocellular carcinoma.Carcinogenesis201435102331233810.1093/carcin/bgu15125031272
     [Google Scholar]
  22. ManchadoE. WeissmuellerS. MorrisJ.P.IV ChenC.C. WullenkordR. LujambioA. de StanchinaE. PoirierJ.T. GainorJ.F. CorcoranR.B. EngelmanJ.A. RudinC.M. RosenN. LoweS.W. A combinatorial strategy for treating KRAS-mutant lung cancer.Nature2016534760964765110.1038/nature1860027338794
     [Google Scholar]
  23. LiF. HuynhH. LiX. RuddyD.A. WangY. OngR. ChowP. QiuS. TamA. RakiecD.P. SchlegelR. MonahanJ.E. HuangA. FGFR-mediated reactivation of MAPK signaling attenuates antitumor effects of imatinib in gastrointestinal stromal tumors.Cancer Discov.20155443845110.1158/2159‑8290.CD‑14‑076325673643
     [Google Scholar]
  24. SinhaS. BoysenJ. NelsonM. WarnerS.L. BearssD. KayN.E. GhoshA.K. Axl activates fibroblast growth factor receptor pathway to potentiate survival signals in B-cell chronic lymphocytic leukemia cells.Leukemia20163061431143610.1038/leu.2015.32326598018
     [Google Scholar]
  25. TurnerN. PearsonA. SharpeR. LambrosM. GeyerF. Lopez-GarciaM.A. NatrajanR. MarchioC. IornsE. MackayA. GillettC. GrigoriadisA. TuttA. Reis-FilhoJ.S. AshworthA. FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer.Cancer Res.20107052085209410.1158/0008‑5472.CAN‑09‑374620179196
     [Google Scholar]
  26. YadavV. ZhangX. LiuJ. EstremS. LiS. GongX.Q. BuchananS. HenryJ.R. StarlingJ.J. PengS.B. Reactivation of mitogen-activated protein kinase (MAPK) pathway by FGF receptor 3 (FGFR3)/Ras mediates resistance to vemurafenib in human B-RAF V600E mutant melanoma.J. Biol. Chem.201228733280872809810.1074/jbc.M112.37721822730329
     [Google Scholar]
  27. PortaR. BoreaR. CoelhoA. KhanS. AraújoA. ReclusaP. FranchinaT. Van Der SteenN. Van DamP. FerriJ. SireraR. NaingA. HongD. RolfoC. FGFR a promising druggable target in cancer: Molecular biology and new drugs.Crit. Rev. Oncol. Hematol.201711325626710.1016/j.critrevonc.2017.02.01828427515
     [Google Scholar]
  28. van RhijnB.W.G. van TilborgA.A.G. LurkinI. BonaventureJ. de VriesA. ThieryJ.P. van der KwastT.H. ZwarthoffE.C. RadvanyiF. Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders.Eur. J. Hum. Genet.2002101281982410.1038/sj.ejhg.520088312461689
     [Google Scholar]
  29. AcevedoV.D. IttmannM. SpencerD.M. Paths of FGFR-driven tumorigenesis.Cell Cycle20098458058810.4161/cc.8.4.765719182515
     [Google Scholar]
  30. RostyC. AubriotM.H. CappellenD. BourdinJ. CartierI. ThieryJ. Sastre-GarauX. RadvanyiF. Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation.Mol. Cancer2005411510.1186/1476‑4598‑4‑1515869706
     [Google Scholar]
  31. HernándezS. de MugaS. AgellL. JuanpereN. EsguevaR. LorenteJ.A. MojalS. SerranoS. LloretaJ. FGFR3 mutations in prostate cancer: Association with low-grade tumors.Mod. Pathol.200922684885610.1038/modpathol.2009.4619377444
     [Google Scholar]
  32. SankarK. GadgeelS.M. QinA. Molecular therapeutic targets in non-small cell lung cancer.Expert Rev. Anticancer Ther.202020864766110.1080/14737140.2020.178715632580596
     [Google Scholar]
  33. ZhangP. YueL. LengQ. ChangC. GanC. YeT. CaoD. Targeting FGFR for cancer therapy.J. Hematol. Oncol.20241713910.1186/s13045‑024‑01558‑138831455
     [Google Scholar]
  34. GospodarowiczD. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth.Nature1974249545312312710.1038/249123a04364816
     [Google Scholar]
  35. BeenkenA. MohammadiM. The FGF family: Biology, pathophysiology and therapy.Nat. Rev. Drug Discov.20098323525310.1038/nrd279219247306
     [Google Scholar]
  36. BelloE. ColellaG. ScarlatoV. OlivaP. BerndtA. ValbusaG. SerraS.C. D’IncalciM. CavallettiE. GiavazziR. DamiaG. CamboniG. E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models.Cancer Res.20117141396140510.1158/0008‑5472.CAN‑10‑270021212416
     [Google Scholar]
  37. GuagnanoV. FuretP. SpankaC. BordasV. Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase.J. Med. Chem.2011547066708310.1021/jm200622221936542
     [Google Scholar]
  38. BrooksA.N. KilgourE. SmithP.D. Molecular pathways: Fibroblast growth factor signaling: A new therapeutic opportunity in cancer.Clin. Cancer Res.20121871855186210.1158/1078‑0432.CCR‑11‑069922388515
     [Google Scholar]
  39. GavineP.R. MooneyL. KilgourE. ThomasA.P. Al-KadhimiK. BeckS. RooneyC. ColemanT. BakerD. MellorM.J. BrooksA.N. KlinowskaT. AZD4547: An orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family.Cancer Res.20127282045205610.1158/0008‑5472.CAN‑11‑303422369928
     [Google Scholar]
  40. OchiiwaH. FujitaH. ItohK. SootomeH. HashimotoA. FujiokaY. NakatsuruY. OdaN. YonekuraK. HiraiH. UtsugiT. Abstract A270: TAS-120, a highly potent and selective irreversible FGFR inhibitor, is effective in tumors harboring various FGFR gene abnormalities.Mol. Cancer Ther.20131211_SupplementA27010.1158/1535‑7163.TARG‑13‑A270
     [Google Scholar]
  41. DransfieldD. LeeJ. WaghorneC. BullC. SavageR.E. ZhaoX. YuanS. ChangE. NakuciE. EathirajS. Cornell-KennonS. GuX. AliS. ChenC-R. Abstract A278: ARQ 087, a multi-tyrosine kinase inhibitor with potent in vitro and in vivo activity in FGFR2 driven models.Mol. Cancer Ther.20131211_SupplementA27810.1158/1535‑7163.TARG‑13‑A278
     [Google Scholar]
  42. NakanishiY. AkiyamaN. TsukaguchiT. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor.Mol Cancer Ther20141311254758
     [Google Scholar]
  43. HéroultM. EllinghausP. SiegC. BrohmD. GruenewaldS. CollinM-P. BoemerU. LobellM. HuebschW. OckerM. InceS. HaegebarthA. JautelatR. Hess-StumppH. BrandsM. ZiegelbauerK. Abstract 1739: Preclinical profile of BAY 1163877 - a selective pan-FGFR inhibitor in phase 1 clinical trial.Cancer Res.20147419_Supplement173910.1158/1538‑7445.AM2014‑1739
     [Google Scholar]
  44. PortaC. GiglioneP. LiguigliW. PaglinoC. Dovitinib (CHIR258, TKI258): Structure, development and preclinical and clinical activity.Future Oncol.2015111395010.2217/fon.14.20825572783
     [Google Scholar]
  45. MarkhamA. Erdafitinib: First global approval.Drugs20197991017102110.1007/s40265‑019‑01142‑931161538
     [Google Scholar]
  46. HoyS.M. Pemigatinib: First approval.Drugs202080992392910.1007/s40265‑020‑01330‑y32472305
     [Google Scholar]
  47. KangC. Infigratinib: First approval.Drugs202181111355136010.1007/s40265‑021‑01567‑134279850
     [Google Scholar]
  48. SyedY.Y. Futibatinib: First approval.Drugs202282181737174310.1007/s40265‑022‑01806‑z36441501
     [Google Scholar]
  49. RenhoweP.A. PecchiS. ShaferC.M. MachajewskiT.D. JazanE.M. TaylorC. Antonios-McCreaW. McBrideC.M. FrazierK. WiesmannM. LapointeG.R. FeuchtP.H. WarneR.L. HeiseC.C. MenezesD. AardalenK. YeH. HeM. LeV. VoraJ. JansenJ.M. Wernette-HammondM.E. HarrisA.L. Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A novel class of receptor tyrosine kinase inhibitors.J. Med. Chem.200952227829210.1021/jm800790t19113866
     [Google Scholar]
  50. GozgitJ.M. WongM.J. MoranL. WardwellS. MohemmadQ.K. NarasimhanN.I. ShakespeareW.C. WangF. ClacksonT. RiveraV.M. Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models.Mol. Cancer Ther.201211369069910.1158/1535‑7163.MCT‑11‑045022238366
     [Google Scholar]
  51. ColellaG. Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors.Ann. Oncol.20142522442251
     [Google Scholar]
  52. RothG.J. HeckelA. ColbatzkyF. HandschuhS. KleyJ. Lehmann-LintzT. LotzR. Tontsch-GruntU. WalterR. HilbergF. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120).J. Med. Chem.200952144466448010.1021/jm900431g19522465
     [Google Scholar]
  53. MohammadiM. McMahonG. SunL. TangC. HirthP. YehB.K. HubbardS.R. SchlessingerJ. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.Science1997276531495596010.1126/science.276.5314.9559139660
     [Google Scholar]
  54. MohammadiM. FroumS. HambyJ.M. SchroederM.C. PanekR.L. LuG.H. EliseenkovaA.V. GreenD. SchlessingerJ. HubbardS.R. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain.EMBO J.199817205896590410.1093/emboj/17.20.58969774334
     [Google Scholar]
  55. HambyJ.M. ConnollyC.J.C. SchroederM.C. WintersR.T. ShowalterH.D.H. PanekR.L. MajorT.C. OlsewskiB. RyanM.J. DahringT. LuG.H. KeiserJ. AmarA. ShenC. KrakerA.J. SlintakV. NelsonJ.M. FryD.W. BradfordL. HallakH. DohertyA.M. Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors.J. Med. Chem.199740152296230310.1021/jm970367n9240345
     [Google Scholar]
  56. NaY.R. KimJ.Y. SongC.H. KimM. DoY.T. VoT.T.L. ChoiE. HaE. SeoJ.H. ShinS.J. The FGFR family inhibitor AZD4547 exerts an antitumor effect in ovarian cancer cells.Int. J. Mol. Sci.202122191081710.3390/ijms22191081734639155
     [Google Scholar]
  57. PlimackE.R. LoRussoP.M. McCoonP. TangW. KrebsA.D. CurtG. EckhardtS.G. AZD1480: A phase I study of a novel JAK2 inhibitor in solid tumors.Oncologist201318781982010.1634/theoncologist.2013‑019823847256
     [Google Scholar]
  58. NogovaL. SequistL.V. Perez GarciaJ.M. AndreF. DelordJ.P. HidalgoM. SchellensJ.H.M. CassierP.A. CamidgeD.R. SchulerM. VaishampayanU. BurrisH.A. TianG.G. CamponeM. WainbergZ.A. LimW.T. LoRussoP. ShapiroG.I. ParkerK. ChenX. ChoudhuryS. RingeisenF. Graus-PortaD. PorterD. IsaacsR. BuettnerR. WolfJ. Evaluation of BGJ398, a fibroblast growth factor receptor 1-3 kinase inhibitor, in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: Results of a global phase I, dose-escalation and dose-expansion study.J. Clin. Oncol.201735215716510.1200/JCO.2016.67.204827870574
     [Google Scholar]
  59. CarterE.P. FearonA.E. GroseR.P. Careless talk costs lives: Fibroblast growth factor receptor signalling and the consequences of pathway malfunction.Trends Cell Biol.201525422123310.1016/j.tcb.2014.11.00325467007
     [Google Scholar]
  60. ChengW. WangM. TianX. ZhangX. An overview of the binding models of FGFR tyrosine kinases in complex with small molecule inhibitors.Eur. J. Med. Chem.201712647649010.1016/j.ejmech.2016.11.05227914362
     [Google Scholar]
  61. TraxlerP. FuretP. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors.Pharmacol. Ther.1999822-319520610.1016/S0163‑7258(98)00044‑810454197
     [Google Scholar]
  62. YosaatmadjaY. PattersonA.V. SmaillJ.B. SquireC.J. The 1.65 Å resolution structure of the complex of AZD4547 with the kinase domain of FGFR1 displays exquisite molecular recognition.Acta Crystallogr. D Biol. Crystallogr.201571352553310.1107/S139900471402753925760602
     [Google Scholar]
  63. PataniH. BunneyT.D. ThiyagarajanN. NormanR.A. OggD. BreedJ. AshfordP. PottertonA. EdwardsM. WilliamsS.V. ThomsonG.S. PangC.S.M. KnowlesM.A. BreezeA.L. OrengoC. PhillipsC. KatanM. Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use.Oncotarget2016717242522426810.18632/oncotarget.813226992226
     [Google Scholar]
  64. EbiikeH. TakaN. MatsushitaM. OhmoriM. TakamiK. HyohdohI. KohchiM. HayaseT. NishiiH. MorikamiK. NakanishiY. AkiyamaN. ShindohH. IshiiN. IsobeT. MatsuokaH. Discovery of [5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone (CH5183284/Debio 1347), an orally available and selective fibroblast growth factor receptor (FGFR) inhibitor.J. Med. Chem.20165923105861060010.1021/acs.jmedchem.6b0115627933954
     [Google Scholar]
  65. LiangG. ChenG. WeiX. ZhaoY. LiX. Small molecule inhibition of fibroblast growth factor receptors in cancer.Cytokine Growth Factor Rev.201324546747510.1016/j.cytogfr.2013.05.00223830577
     [Google Scholar]
  66. RoskoskiR.Jr Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes.Pharmacol. Res.2016103264810.1016/j.phrs.2015.10.02126529477
     [Google Scholar]
  67. TuckerJ.A. KleinT. BreedJ. BreezeA.L. OvermanR. PhillipsC. NormanR.A. Structural insights into FGFR kinase isoform selectivity: Diverse binding modes of AZD4547 and ponatinib in complex with FGFR1 and FGFR4.Structure201422121764177410.1016/j.str.2014.09.01925465127
     [Google Scholar]
  68. KufarevaI. AbagyanR. Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states.J. Med. Chem.200851247921793210.1021/jm801029919053777
     [Google Scholar]
  69. TsimafeyeuI. DaeyaertF. YinW. Ludes-MeyersJ. ByakhovM. TjulandinS. 476 FGFR2 targeting with allosteric inhibitor RPT835.Eur. J. Cancer20145015510.1016/S0959‑8049(14)70602‑1
     [Google Scholar]
  70. HahJ.M. SharmaV. LiH. LawrenceD.S. Acquisition of a “Group A”-selective Src kinase inhibitor via a global targeting strategy.J. Am. Chem. Soc.2006128185996599710.1021/ja060136i16669643
     [Google Scholar]
  71. HillZ.B. PereraB.G.K. MalyD.J. A chemical genetic method for generating bivalent inhibitors of protein kinases.J. Am. Chem. Soc.2009131196686668810.1021/ja900871y19391594
     [Google Scholar]
  72. LambaV. GhoshI. New directions in targeting protein kinases: Focusing upon true allosteric and bivalent inhibitors.Curr. Pharm. Des.201218202936294510.2174/13816121280067281322571662
     [Google Scholar]
  73. WeiM. PengX. XingL. DaiY. HuangR. GengM. ZhangA. AiJ. SongZ. Design, synthesis and biological evaluation of a series of novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine derivatives as potent fibroblast growth factor receptor (FGFR) inhibitors.Eur. J. Med. Chem.201815492810.1016/j.ejmech.2018.05.00529775937
     [Google Scholar]
  74. ZhangX. WangY. JiJ. SiD. BaoX. YuZ. ZhuY. ZhaoL. LiW. LiuJ. Discovery of 1,6-naphthyridin-2(1H)-one derivatives as novel, potent, and selective FGFR4 inhibitors for the treatment of hepatocellular carcinoma.J. Med. Chem.202265117595761810.1021/acs.jmedchem.1c0197735635004
     [Google Scholar]
  75. ZhangZ. LiJ. ChenH. HuangJ. SongX. TuZ.C. ZhangZ. PengL. ZhouY. DingK. Design, synthesis, and biological evaluation of 2 formyl tetrahydronaphthyridine urea derivatives as new selective covalently reversible FGFR4 inhibitors.J. Med. Chem.20226543249326510.1021/acs.jmedchem.1c0181635119278
     [Google Scholar]
  76. ModhD.H. ModiS.J. DeokarH. YadavS. KulkarniV.M. Fibroblast growth factor receptor (FGFR) inhibitors as anticancer agents: 3D-QSAR, molecular docking and dynamics simulation studies of 1, 6-naphthyridines and pyridopyrimidines.J. Biomol. Struct. Dyn.20234183591360610.1080/07391102.2022.205320635318898
     [Google Scholar]
  77. RanK. ZengJ. WanG. HeX. FengZ. XiangW. WeiW. HuX. WangN. LiuZ. YuL. Design, synthesis and biological evaluations of a series of Pyrido[1,2-a]pyrimidinone derivatives as novel selective FGFR inhibitors.Eur. J. Med. Chem.202122011349910.1016/j.ejmech.2021.11349933940465
     [Google Scholar]
  78. WeiY. TangY. ZhouY. YangY. CuiY. WangX. WangY. LiuY. LiuN. WangQ. LiC. RuanH. ZhouH. WeiM. YangG. YangC. Discovery and optimization of a novel 2H-pyrazolo[3,4-d]pyrimidine derivative as a potent irreversible pan-fibroblast growth factor receptor inhibitor imp discovery of potent irreversible pan-fibroblast growth factor receptor (FGFR) inhibitors.J. Med. Chem.202164139078909910.1021/acs.jmedchem.1c0017434129329
     [Google Scholar]
  79. XieW. YangS. LiangL. WangM. ZuoW. LeiY. ZhangY. TangW. LuT. ChenY. JiangY. discovery of 2-amino-7-sulfonyl-7h-pyrrolo[2,3-d]pyrimidine derivatives as potent reversible FGFR inhibitors with gatekeeper mutation tolerance: Design, synthesis, and biological evaluation.J. Med. Chem.20226524165701658810.1021/acs.jmedchem.2c0142036480917
     [Google Scholar]
  80. WuL. ZhangC. HeC. QianD. LuL. SunY. XuM. ZhuoJ. LiuP.C.C. KlabeR. WynnR. CovingtonM. GallagherK. LeffetL. BowmanK. DiamondS. KoblishH. ZhangY. SolovievM. HollisG. BurnT.C. ScherleP. YeleswaramS. HuberR. YaoW. Discovery of pemigatinib: A potent and selective fibroblast growth factor receptor (FGFR) inhibitor.J. Med. Chem.20216415106661067910.1021/acs.jmedchem.1c0071334269576
     [Google Scholar]
  81. LiC. DaiY. KongX. WangB. PengX. WuH. ShenY. YangY. JiY. WangD. LiS. LiX. ShiY. GengM. ZhengM. AiJ. LiuH. Structural optimization of fibroblast growth factor receptor inhibitors for treating solid tumors.J. Med. Chem.20236653226324910.1021/acs.jmedchem.2c0150736802596
     [Google Scholar]
  82. ShvartsbartA. RoachJ.J. WittenM.R. KoblishH. HarrisJ.J. CovingtonM. HessR. LinL. FrascellaM. TruongL. LeffetL. ConlenP. BeshadE. KlabeR. KatiyarK. KaldonL. Young-SciameR. HeX. PetuskyS. ChenK.J. HorseyA. LeiH.T. EplingL.B. DellerM.C. VechorkinO. YaoW. Discovery of potent and selective inhibitors of wild-type and gatekeeper mutant fibroblast growth factor receptor (FGFR) 2/3.J. Med. Chem.20226522154331544210.1021/acs.jmedchem.2c0136636356320
     [Google Scholar]
  83. WangY. DaiY. WuX. LiF. LiuB. LiC. LiuQ. ZhouY. WangB. ZhuM. CuiR. TanX. XiongZ. LiuJ. TanM. XuY. GengM. JiangH. LiuH. AiJ. ZhengM. Discovery and development of a series of pyrazolo[3,4-d]pyridazinone compounds as the novel covalent fibroblast growth factor receptor inhibitors by the rational drug design.J. Med. Chem.201962167473748810.1021/acs.jmedchem.9b0051031335138
     [Google Scholar]
  84. ChenX. LiuY. ZhangL. ChenD. DongZ. ZhaoC. LiuZ. XiaQ. WuJ. ChenY. ZhengX. CaiY. Design, synthesis, and biological evaluation of indazole derivatives as selective and potent FGFR4 inhibitors for the treatment of FGF19-driven hepatocellular cancer.Eur. J. Med. Chem.202121411321910.1016/j.ejmech.2021.11321933618175
     [Google Scholar]
  85. ShaoM. ChenX. YangF. SongX. ZhouY. LinQ. FuY. OrtegaR. LinX. TuZ. PattersonA.V. SmaillJ.B. ChenY. LuX. Design, synthesis, and biological evaluation of aminoindazole derivatives as highly selective covalent inhibitors of wild-type and gatekeeper mutant FGFR4.J. Med. Chem.20226565113513310.1021/acs.jmedchem.2c0009635271262
     [Google Scholar]
  86. ZhongZ. ShiL. FuT. HuangJ. PanZ. Discovery of novel 7-azaindole derivatives as selective covalent fibroblast growth factor receptor 4 inhibitors for the treatment of hepatocellular carcinoma.J. Med. Chem.202265107278729510.1021/acs.jmedchem.2c0025535549181
     [Google Scholar]
  87. EldehnaW.M. El KerdawyA.M. Al-AnsaryG.H. Al-RashoodS.T. AliM.M. MahmoudA.E. Type IIA - Type IIB protein tyrosine kinase inhibitors hybridization as an efficient approach for potent multikinase inhibitor development: Design, synthesis, anti-proliferative activity, multikinase inhibitory activity and molecular modeling of novel indolinone-based ureides and amides.Eur. J. Med. Chem.2019163375310.1016/j.ejmech.2018.11.06130503942
     [Google Scholar]
  88. TakamuraT. HorinakaM. YasudaS. ToriyamaS. AonoY. SowaY. MikiT. UkimuraO. SakaiT. FGFR inhibitor BGJ398 and HDAC inhibitor OBP-801 synergistically inhibit cell growth and induce apoptosis in bladder cancer cells.Oncol. Rep.201839262763229207153
     [Google Scholar]
  89. WanG. FengZ. ZhangQ. LiX. RanK. FengH. LuoT. ZhouS. SuC. WeiW. WangN. GaoC. ZhaoL. YuL. Design and synthesis of fibroblast growth factor receptor (FGFR) and histone deacetylase (HDAC) dual inhibitors for the treatment of cancer.J. Med. Chem.20226524165411656910.1021/acs.jmedchem.2c0141336449947
     [Google Scholar]
  90. PanC. NieW. WangJ. DuJ. PanZ. GaoJ. LuY. CheJ. ZhuH. DaiH. ChenB. HeQ. DongX. Design, synthesis and biological evaluation of quinazoline derivatives as potent and selective FGFR4 inhibitors.Eur. J. Med. Chem.202122511379410.1016/j.ejmech.2021.11379434488024
     [Google Scholar]
  91. YangF. ChenX. SongX. OrtegaR. LinX. DengW. GuoJ. TuZ. PattersonA.V. SmaillJ.B. ChenY. LuX. Design, synthesis, and biological evaluation of 5-formyl pyrrolo[ 3,2-b]pyridine-3-carboxamides as new selective, potent, and reversible-covalent FGFR4 inhibitors.J. Med. Chem.20226521148091483110.1021/acs.jmedchem.2c0131936278929
     [Google Scholar]
  92. YamaniA. Zdżalik-BieleckaD. LipnerJ. StańczakA. PiórkowskaN. StańczakP.S. OlejkowskaP. Hucz-KalitowskaJ. MagdyczM. DzwonekK. DubielK. Lamparska-PrzybyszM. PopielD. PieczykolanJ. WieczorekM. Discovery and optimization of novel pyrazole-benzimidazole CPL304110, as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1–3).Eur. J. Med. Chem.202121011299010.1016/j.ejmech.2020.11299033199155
     [Google Scholar]
  93. YingS. DuX. FuW. YunD. ChenL. CaiY. XuQ. WuJ. LiW. LiangG. Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth factor receptor 1 inhibitors for the treatment of gastric cancer.Eur. J. Med. Chem.201712788589910.1016/j.ejmech.2016.10.06627829519
     [Google Scholar]
  94. MaL. LiY. LuoR. WangY. CaoJ. FuW. QianB. ZhengL. TangL. LvX. ZhengL. LiangG. ChenL. Discovery of a selective and orally bioavailable FGFR2 degrader for treating gastric cancer.J. Med. Chem.202366117438745310.1021/acs.jmedchem.3c0015037220310
     [Google Scholar]
/content/journals/acamc/10.2174/0118715206318833240819031953
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A Promising Paradigm Shift in Cancer Treatment with FGFR Inhibitors
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 2 (2025); https://doi.org/10.2174/0118715206318833240819031953
/content/journals/acamc/10.2174/0118715206318833240819031953
/content/journals/acamc/10.2174/0118715206318833240819031953
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  • Article Type:     Review Article
Keyword(s): angiogenesis; anticancer; FGFR; heterocyclic; potency; SAR

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