Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer

References

• Makohon-MooreAIacobuzio-DonahueCAPancreatic cancer biology and genetics from an evolutionary perspectiveNat Rev Cancer2016169 553 56527444064
   PubMed Web of Science ®Google Scholar
• HidalgoMPancreatic cancerN Engl J Med201036217 1605 161720427809
   PubMed Web of Science ®Google Scholar
• SiegelRLMillerKDJemalACancer statistics, 2016CA Cancer J Clin2016661 7 3026742998
   PubMed Web of Science ®Google Scholar
• KamisawaTWoodLDItoiTTakaoriKPancreatic cancerLancet201638810039 73 8526830752
   PubMed Web of Science ®Google Scholar
• VincentAHermanJSchulickRHrubanRHGogginsMPancreatic cancerLancet20113789791 607 62021620466
   PubMed Web of Science ®Google Scholar
• CollocaGVenturinoAGuarneriDAnalysis of response-related and time-to-event endpoints in randomized trials of gemcitabine-based treatment versus gemcitabine alone as first-line treatment of patients with advanced pancreatic cancerClin Colorectal Canc2016153 264 276
   Web of Science ®Google Scholar
• XiangXZhangLLiJA phase II study of biweekly gemcitabine at fixed dose rate infusion plus S1 as first-line chemotherapy in patients with locally advanced or metastatic pancreatic cancerJ Clin Oncol2016344 S357
   Web of Science ®Google Scholar
• JuHQGochoTAguilarMMechanisms of overcoming intrinsic resistance to gemcitabine in pancreatic ductal adenocarcinoma through the redox modulationMol Cancer Ther2015143 788 79825527634
   PubMed Web of Science ®Google Scholar
• WeizmanNKrelinYShabtay-OrbachAMacrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminaseOncogene20143329 3812 381923995783
   PubMed Web of Science ®Google Scholar
• HillRRabbMMadureiraPAGemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapyCell Death Dis20134 e79124008735
   PubMed Web of Science ®Google Scholar
• HammelPHuguetFvan LaethemJLEffect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib the LAP07 randomized clinical trialJAMA201631517 1844 185327139057
   PubMed Web of Science ®Google Scholar
• CatenacciDVTJunttilaMRKarrisonTRandomized phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancerJ Clin Oncol20153336 4284 429226527777
   PubMed Web of Science ®Google Scholar
• KobayashiSUenoMHaraHUnexpected side effects of a high S-1 dose: subanalysis of a phase III trial comparing gemcitabine, S-1 and combinatorial treatments for advanced pancreatic cancerOncology2016913 117 12627303788
   PubMed Web of Science ®Google Scholar
• PrabhuLMundadeRKorcMLoehrerPJLuTCritical role of NF-kappa B in pancreatic cancerOncotarget2014522 10969 1097525473891
   PubMedGoogle Scholar
• RadhakrishnanPBryantVCBlowersECTargeting the NF-kappa B and mTOR pathways with a quinoxaline urea analog that inhibits IKK beta for pancreas cancer therapyClin Cancer Res2013198 2025 203523444213
   PubMed Web of Science ®Google Scholar
• GambleCMcIntoshKScottRInhibitory kappa B kinases as targets for pharmacological regulationBr J Pharmacol20121654 802 81921797846
   PubMed Web of Science ®Google Scholar
• XuGLoYCLiQCrystal structure of inhibitor of kappaB kinase betaNature20114727343 325 33021423167
   PubMed Web of Science ®Google Scholar
• WuHWWangGHWangZWA negative feedback loop between miR-200b and the nuclear factor-kappa B pathway via IKBKB/IKK-beta in breast cancer cellsFEBS J201628312 2259 227126433127
   PubMed Web of Science ®Google Scholar
• SakamotoKHikibaYNakagawaHInhibitor of kappaB kinase beta regulates gastric carcinogenesis via interleukin-1alpha expressionGastroenterology20101391 226 23820347815
   PubMed Web of Science ®Google Scholar
• KoppeCGautheronJVucurMA new molecular interaction between IKK alpha/beta and RIPK1 regulates biliary homeostasis and hepatocarcinogenesisHepatology2016631 suppl 257a 258a
   Google Scholar
• GretenFRArkanMCBollrathJNF-kappa B is a negative regulator of IL-1 beta secretion as revealed by genetic and pharmacological inhibition of IKK betaCell20071305 918 93117803913
   PubMed Web of Science ®Google Scholar
• WilsonWBaldwinASMaintenance of constitutive I kappa B kinase activity by glycogen synthase kinase-3 alpha/beta in pancreatic cancerCancer Res20086819 8156 816318829575
   PubMed Web of Science ®Google Scholar
• WeichertWBoehmMGekelerVHigh expression of RelA/p65 is associated with activation of nuclear factor-kappa B-dependent signaling in pancreatic cancer and marks a patient population with poor prognosisBr J Cancer2007974 523 53017622249
   PubMed Web of Science ®Google Scholar
• LingJKangYZhaoRKrasG12D-induced IKK2/beta/NF-kappaB activation by IL-1alpha and p62 feedforward loops is required for development of pancreatic ductal adenocarcinomaCancer Cell2012211 105 12022264792
   PubMed Web of Science ®Google Scholar
• HolcomBYip-SchneiderMSchmidtCMThe role of nuclear factor kappa B in pancreatic cancer and the clinical applications of targeted therapyPancreas2008363 225 23518362834
   PubMed Web of Science ®Google Scholar
• ArkanMCGretenFRIKK- and NF-kappa B-mediated functions in carcinogenesisCurr Top Microbiol Immunol2011349 159 16920845109
   PubMed Web of Science ®Google Scholar
• ManiatiEBossardMCookNCrosstalk between the canonical NF-kappa B and Notch signaling pathways inhibits Ppar gamma expression and promotes pancreatic cancer progression in miceJ Clin Invest201112112 4685 469922056382
   PubMed Web of Science ®Google Scholar
• GaddipatiSLuQXKasettiRBIKK2 inhibition using TPCA-1-loaded PLGA microparticles attenuates laser-induced chor-oidal neovascularization and macrophage recruitmentPLoS One2015103 e012118525803615
   PubMed Web of Science ®Google Scholar
• BergerAQuastSAPlotzMKammermeierAEberleJSensitization of melanoma cells for TRAIL-induced apoptosis by BMS-345541 correlates with altered phosphorylation and activation of BaxCell Death Dis20134 e47723348591
   PubMed Web of Science ®Google Scholar
• MilesRRWaxmanIVan Den VenCBortezomib (BTZ), IKK inhibitor ML120B, and combination therapy induce apoptosis, inhibit NF-kappa B activation, and decrease specific proteins in primary mediastinal B-cell lymphoma (PMBL)Ann Oncol201122 133
   Web of Science ®Google Scholar
• HuangJJChuHXJiangZYRecent advances in the structure-based and ligand-based design of IKK beta inhibitors as anti-inflammation and anti-cancer agentsCurr Med Chem20142134 3893 391725139725
   PubMed Web of Science ®Google Scholar
• LiLAggarwalBBShishodiaSAbbruzzeseJKurzrockRNuclear factor-kappa B and I kappa B kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloyl-methane) is associated with the suppression of proliferation and the induction of apoptosisCancer200410110 2351 236215476283
   PubMed Web of Science ®Google Scholar
• AggarwalBBSungBPharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targetsTrends Pharmacol Sci2009302 85 9419110321
   PubMed Web of Science ®Google Scholar
• KasinskiALDuYHThomasSLInhibition of I kappa B kinase-nuclear factor-kappa B signaling pathway by 3,5-bis(2-flurobenzylidene) piperidin-4-one (EF24), a novel monoketone analog of curcuminMol Pharmacol2008743 654 66118577686
   PubMed Web of Science ®Google Scholar
• OliveraAMooreTWHuFInhibition of the NF-kappa B signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer propertiesInt Immunopharmacol2012122 368 37722197802
   PubMed Web of Science ®Google Scholar
• LagisettyPSubramaniamDSahooKAnantSAwasthiVAnticancer activity of an imageable curcuminoid 1-[2-Aminoethyl-(6-hydrazinopyridine-3-carbamidyl)-3,5-bis-(2-fluorobenzylidene)-4-piperidone (EFAH)Chem Biol Drug Des2012792 194 20122107757
   PubMed Web of Science ®Google Scholar
• NagarajuGPZhuSJWenJNovel synthetic curcumin analogues EF31 and UBS109 are potent DNA hypomethylating agents in pancreatic cancerCancer Lett20133412 195 20323933177
   PubMed Web of Science ®Google Scholar
• MorrisGMHueyRLindstromWAutoDock4 and AutoDock-Tools4: automated docking with selective receptor flexibilityJ Comput Chem20093016 2785 279119399780
   PubMed Web of Science ®Google Scholar
• LiuSPMisquittaYROllandACrystal structure of a human I kappa B kinase beta asymmetric dimerJ Biol Chem201328831 22758 2276723792959
   PubMed Web of Science ®Google Scholar
• WangJMWangWKollmanPAAntechamber: an accessory software package for molecular mechanical calculationsAbstr Pap Am Chem Soc2001222 U403
   Web of Science ®Google Scholar
• IzaguirreJACatarelloDPWozniakJMSkeelRDLangevin stabilization of molecular dynamicsJ Chem Phys20011145 2090 2098
   Web of Science ®Google Scholar
• KrautlerVVan GunsterenWFHunenbergerPHA fast SHAKE: algorithm to solve distance constraint equations for small molecules in molecular dynamics simulationsJ Comput Chem2001225 501 508
   Web of Science ®Google Scholar
• ShanYKlepeisJLEastwoodMPDrorROShawDEGaussian split Ewald: a fast Ewald mesh method for molecular simulationJ Chem Phys20051225 5410115740304
   PubMed Web of Science ®Google Scholar
• KuhnBGerberPSchulz-GaschTStahlMValidation and use of the MM-PBSA approach for drug discoveryJ Med Chem20054812 4040 404815943477
   PubMed Web of Science ®Google Scholar
• MillerBR3rdMcGeeTDJrSwailsJMHomeyerNGohlkeHRoitbergAEMMPBSA.py: an efficient program for end-state free energy calculationsJ Chem Theory Comput201289 3314 332126605738
   PubMed Web of Science ®Google Scholar
• HoeselBSchmidJAThe complexity of NF-kappa B signaling in inflammation and cancerMol Cancer201312 8623915189
   PubMed Web of Science ®Google Scholar
• WolfgangCLHermanJMLaheruDARecent progress in pancreatic cancerCA Cancer J Clin2013635 318 34823856911
   PubMed Web of Science ®Google Scholar
• SinghDUpadhyayGSrivastavaRKShankarSRecent advances in pancreatic cancer: biology, treatment, and preventionBiochim Biophys Acta201518561 13 2725977074
   PubMed Web of Science ®Google Scholar
• LongJZhangYQYuXJOvercoming drug resistance in pancreatic cancerExpert Opin Ther Targets2011157 817 82821391891
   PubMed Web of Science ®Google Scholar
• LiYWVandenBoomTGWangZWmiR-146a suppresses invasion of pancreatic cancer cellsCancer Res2010704 1486 149520124483
   PubMed Web of Science ®Google Scholar
• XiaYFYeddulaNLeblancMReduced cell proliferation by IKK2 depletion in a mouse lung-cancer modelNat Cell Biol2012143 257 26622327365
   PubMed Web of Science ®Google Scholar
• WuDGYuPLiJWApigenin potentiates the growth inhibitory effects by IKK-beta-mediated NF-kappa B activation in pancreatic cancer cellsToxicol Lett20142241 157 16424148603
   PubMed Web of Science ®Google Scholar
• LeungCHChanDSHLiYWFongWFMaDLHit identification of IKK beta natural product inhibitorBMC Pharmacol Toxicol201314 323294515
   PubMed Web of Science ®Google Scholar
• LiYWEllisKLAliSApoptosis-inducing effect of chemotherapeutic agents is potentiated by soy isoflavone genistein, a natural inhibitor of NF-kappa B in BxPC-3 pancreatic cancer cell linePancreas2004284 E90 E9515097869
   PubMed Web of Science ®Google Scholar
• DhillonNAggarwalBBNewmanRAPhase II trial of cur-cumin in patients with advanced pancreatic cancerClin Cancer Res20081414 4491 449918628464
   PubMed Web of Science ®Google Scholar
• WuPNielsenTEClausenMHFDA-approved small-molecule kinase inhibitorsTrends Pharmacol Sci2015367 422 43925975227
   PubMed Web of Science ®Google Scholar
• ZhangJMYangPLGrayNSTargeting cancer with small molecule kinase inhibitorsNat Rev Cancer200991 28 3919104514
   PubMed Web of Science ®Google Scholar