000205428 001__ 205428
000205428 005__ 20250730145102.0
000205428 0247_ $$2doi$$a10.1021/jm501003k
000205428 0247_ $$2ISSN$$a0022-2623
000205428 0247_ $$2ISSN$$a0095-9065
000205428 0247_ $$2ISSN$$a1520-4804
000205428 0247_ $$2ISSN$$a1943-2992
000205428 0247_ $$2WOS$$aWOS:000345722200015
000205428 0247_ $$2pmid$$apmid:25358084
000205428 0247_ $$2altmetric$$aaltmetric:17985526
000205428 0247_ $$2openalex$$aopenalex:W2142928298
000205428 037__ $$aPUBDB-2015-00005
000205428 041__ $$aEnglish
000205428 082__ $$a540
000205428 1001_ $$0P:(DE-HGF)0$$aDudutienė, Virginija$$b0
000205428 245__ $$aDiscovery and Characterization of Novel Selective Inhibitors of Carbonic Anhydrase IX
000205428 260__ $$aWashington, DC$$bACS$$c2014
000205428 3367_ $$00$$2EndNote$$aJournal Article
000205428 3367_ $$2DRIVER$$aarticle
000205428 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1434541878_1343
000205428 3367_ $$2BibTeX$$aARTICLE
000205428 500__ $$3POF3_Assignment on 2016-02-15
000205428 500__ $$3POF3_Prefill: G:(DE-HGF)POF3-6215
000205428 500__ $$a(c) American Chemical Society. Post referee full text in progress. Embargo for full text 1 year from October 30, 2014.
000205428 520__ $$aHuman carbonic anhydrase IX (CA IX) is highly expressedin tumor tissues, and its selective inhibition provides a potential target forthe treatment of numerous cancers. Development of potent, highlyselective inhibitors against this target remains an unmet need in anticancertherapeutics. A series of fluorinated benzenesulfonamides with sub-stituents on the benzene ring was designed and synthesized. Several ofthese exhibited a highly potent and selective inhibition profile against CAIX. Three fluorine atoms significantly increased the affinity by withdrawing electrons and lowering the pKa of thebenzenesulfonamide group. The bulky ortho substituents, such as cyclooctyl or even cyclododecyl groups, fit into thehydrophobic pocket in the active site of CA IX but not CA II, as shown by the compound’s co-crystal structure with chimeric CAIX. The strongest inhibitor of recombinant human CA IX’s catalytic domain in human cells achieved an affinity of 50 pM.However, the high affinity diminished the selectivity. The most selective compound for CA IX exhibited 10 nM affinity. Thecompound that showed the best balance between affinity and selectivity bound with 1 nM affinity. The inhibitors described inthis work provide the basis for novel anticancer therapeutics targeting CA IX.
000205428 536__ $$0G:(DE-H253)POF2-P13-20130405$$aPETRA Beamline P13 (POF2-54G14)$$cPOF2-54G14$$fPOF II$$x0
000205428 536__ $$0G:(DE-H253)POF2-P14-20130405$$aPETRA Beamline P14 (POF2-54G14)$$cPOF2-54G14$$fPOF II$$x1
000205428 588__ $$aDataset connected to CrossRef, bib-pubdb1.desy.de
000205428 693__ $$0EXP:(DE-H253)P-P13-20150101$$1EXP:(DE-H253)PETRAIII-20150101$$6EXP:(DE-H253)P-P13-20150101$$aPETRA III$$fPETRA Beamline P13$$x0
000205428 693__ $$0EXP:(DE-H253)P-P14-20150101$$1EXP:(DE-H253)PETRAIII-20150101$$6EXP:(DE-H253)P-P14-20150101$$aPETRA III$$fPETRA Beamline P14$$x1
000205428 7001_ $$0P:(DE-HGF)0$$aMatulienė, Jurgita$$b1
000205428 7001_ $$0P:(DE-H253)PIP1018767$$aSmirnov, Alexey$$b2
000205428 7001_ $$0P:(DE-HGF)0$$aTimm, David D.$$b3
000205428 7001_ $$0P:(DE-HGF)0$$aZubrienė, Asta$$b4
000205428 7001_ $$0P:(DE-HGF)0$$aBaranauskienė, Lina$$b5
000205428 7001_ $$0P:(DE-HGF)0$$aMorku̅naitė, Vaida$$b6
000205428 7001_ $$0P:(DE-HGF)0$$aSmirnovienė, Joana$$b7
000205428 7001_ $$0P:(DE-HGF)0$$aMichailovienė, Vilma$$b8
000205428 7001_ $$0P:(DE-HGF)0$$aJuozapaitienė, Vaida$$b9
000205428 7001_ $$0P:(DE-HGF)0$$aMickevičiu̅tė, Aurelija$$b10
000205428 7001_ $$0P:(DE-HGF)0$$aKazokaitė, Justina$$b11
000205428 7001_ $$0P:(DE-HGF)0$$aBakšytė, Sandra$$b12
000205428 7001_ $$0P:(DE-HGF)0$$aKasiliauskaitė, Aistė$$b13
000205428 7001_ $$0P:(DE-HGF)0$$aJachno, Jelena$$b14
000205428 7001_ $$0P:(DE-HGF)0$$aRevuckienė, Jurgita$$b15
000205428 7001_ $$0P:(DE-HGF)0$$aKišonaitė, Miglė$$b16
000205428 7001_ $$0P:(DE-HGF)0$$aPilipuitytė, Vilma$$b17
000205428 7001_ $$0P:(DE-HGF)0$$aIvanauskaitė, Eglė$$b18
000205428 7001_ $$0P:(DE-HGF)0$$aMilinavičiu̅tė, Goda$$b19
000205428 7001_ $$0P:(DE-HGF)0$$aSmirnovas, Vytautas$$b20
000205428 7001_ $$0P:(DE-HGF)0$$aPetrikaitė, Vilma$$b21
000205428 7001_ $$0P:(DE-HGF)0$$aKairys, Visvaldas$$b22
000205428 7001_ $$0P:(DE-HGF)0$$aPetrauskas, Vytautas$$b23
000205428 7001_ $$0P:(DE-HGF)0$$aNorvaišas, Povilas$$b24
000205428 7001_ $$0P:(DE-HGF)0$$aLingė, Darius$$b25
000205428 7001_ $$0P:(DE-HGF)0$$aGibieža, Paulius$$b26
000205428 7001_ $$0P:(DE-HGF)0$$aČapkauskaitė, Edita$$b27
000205428 7001_ $$0P:(DE-HGF)0$$aZakšauskas, Audrius$$b28
000205428 7001_ $$0P:(DE-HGF)0$$aKazlauskas, Egidijus$$b29
000205428 7001_ $$0P:(DE-H253)PIP1017370$$aManakova, Elena$$b30
000205428 7001_ $$0P:(DE-H253)PIP1018629$$aGražulis, Saulius$$b31
000205428 7001_ $$0P:(DE-HGF)0$$aLadbury, John E.$$b32
000205428 7001_ $$0P:(DE-HGF)0$$aMatulis, Daumantas$$b33$$eCorresponding author
000205428 773__ $$0PERI:(DE-600)1491411-6$$a10.1021/jm501003k$$gVol. 57, no. 22, p. 9435 - 9446$$n22$$p9435 - 9446$$tJournal of medicinal chemistry$$v57$$x1520-4804$$y2014
000205428 8564_ $$uhttps://bib-pubdb1.desy.de/record/205428/files/10.1021_jm501003k.pdf$$yRestricted
000205428 8564_ $$uhttps://bib-pubdb1.desy.de/record/205428/files/10.1021_jm501003k.gif?subformat=icon$$xicon$$yRestricted
000205428 8564_ $$uhttps://bib-pubdb1.desy.de/record/205428/files/10.1021_jm501003k.jpg?subformat=icon-1440$$xicon-1440$$yRestricted
000205428 8564_ $$uhttps://bib-pubdb1.desy.de/record/205428/files/10.1021_jm501003k.jpg?subformat=icon-180$$xicon-180$$yRestricted
000205428 8564_ $$uhttps://bib-pubdb1.desy.de/record/205428/files/10.1021_jm501003k.jpg?subformat=icon-640$$xicon-640$$yRestricted
000205428 8564_ $$uhttps://bib-pubdb1.desy.de/record/205428/files/10.1021_jm501003k.jpg?subformat=icon-700$$xicon-700$$yRestricted
000205428 8564_ $$uhttps://bib-pubdb1.desy.de/record/205428/files/10.1021_jm501003k.pdf?subformat=pdfa$$xpdfa$$yRestricted
000205428 909CO $$ooai:bib-pubdb1.desy.de:205428$$pVDB
000205428 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1018767$$aExternes Institut$$b2$$k>Extern
000205428 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1017370$$aExternes Institut$$b30$$k>Extern
000205428 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1018629$$aExternes Institut$$b31$$k>Extern
000205428 9132_ $$0G:(DE-HGF)POF3-621$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$9G:(DE-HGF)POF3-6215$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vIn-house research on the structure, dynamics and function of matter$$x0
000205428 9132_ $$0G:(DE-HGF)POF3-622$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$9G:(DE-HGF)POF3-6G3$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vFacility topic: Research on Matter with Brilliant Light Sources$$x1
000205428 9131_ $$0G:(DE-HGF)POF2-54G14$$1G:(DE-HGF)POF2-540$$2G:(DE-HGF)POF2-500$$3G:(DE-HGF)POF2$$4G:(DE-HGF)POF$$9G:(DE-H253)POF2-P13-20130405$$aDE-H253$$bStruktur der Materie$$lForschung mit Photonen, Neutronen, Ionen$$vPETRA III$$x0
000205428 9131_ $$0G:(DE-HGF)POF2-54G14$$1G:(DE-HGF)POF2-540$$2G:(DE-HGF)POF2-500$$3G:(DE-HGF)POF2$$4G:(DE-HGF)POF$$9G:(DE-H253)POF2-P14-20130405$$aDE-H253$$bStruktur der Materie$$lForschung mit Photonen, Neutronen, Ionen$$vPETRA III$$x1
000205428 9141_ $$y2014
000205428 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR
000205428 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000205428 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000205428 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000205428 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000205428 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000205428 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000205428 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000205428 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000205428 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000205428 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000205428 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5
000205428 9201_ $$0I:(DE-H253)EMBL-User-20120814$$kEMBL-User$$lEMBL-User$$x0
000205428 980__ $$ajournal
000205428 980__ $$aVDB
000205428 980__ $$aI:(DE-H253)EMBL-User-20120814
000205428 980__ $$aUNRESTRICTED