Selective inhibition of mutant isocitrate dehydrogenase 1 (IDH1) via disruption of a metal binding network by an allosteric small molecule

Journal of Biological Chemistry

Volumn 290, Issue 2, 2015, Pages 762-774

  Deng, Gejing ^a   Shen, Junqing ^a   Yin, Ming ^a   McManus, Jessica ^a   Mathieu, Magali ^b   Gee, Patricia ^a   He, Timothy ^a   Shi, Chaomei ^a   Bedel, Olivier ^a   McLean, Larry R ^c   Le Strat, Frank ^b   Zhang, Ying ^c   Marquette, Jean Pierre ^b   Gao, Qiang ^a   Zhang, Bailin ^a   Rak, Alexey ^b   Hoffmann, Dietmar ^a   Rooney, Eamonn ^b   Vassort, Aurelie ^b   Englaro, Walter ^b   Li, Yi ^c   Patel, Vinod ^c   Adrian, Francisco ^a   Gross, Stefan ^a   Wiederschain, Dmitri ^a   Cheng, Hong ^a   Licht, Stuart ^a   more..

^a Sanofi Aventis   (United States)

^b SANOFI   (France)

^c Division of Lead Generation and Compound Realization Sanofi   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CRYSTAL STRUCTURE; DIMERS; DISEASES; ENZYMES; POSITIVE IONS; THROUGHPUT;

BIOPHYSICAL STUDIES; CANCER THERAPEUTICS; ENZYMATIC ACTIVITIES; HIGH-THROUGHPUT SCREENS; ISOCITRATE DEHYDROGENASE; SELECTIVE INHIBITION; SELECTIVE INHIBITORS; STEADY-STATE KINETICS;

ENZYME INHIBITION;

2 HYDROXYGLUTARIC ACID; 2 [2 [1H BENZO[D]IMIDAZOL 1 YL] N (3 FLUOROPHENYL)ACETAMIDO] N CYCLOHEXYL 2 (O TOLYL)ACETAMIDE; BIS IMIDAZOLE PHENOL; ENZYME INHIBITOR; ISOCITRATE DEHYDROGENASE 1; ISOCITRATE DEHYDROGENASE 2; MAGNESIUM ION; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; UNCLASSIFIED DRUG; IDH1 PROTEIN, HUMAN; ISOCITRATE DEHYDROGENASE; ISOCITRATE DEHYDROGENASE 2, HUMAN; MAGNESIUM; MUTANT PROTEIN;

ALLOSTERISM; ARTICLE; BINDING AFFINITY; BINDING SITE; CANCER CELL LINE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DIFFERENTIAL SCANNING FLUORIMETRY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ENANTIOMER; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; FLUOROMETRY; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; LIGAND BINDING; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METAL BINDING; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PURIFICATION; PROTON NUCLEAR MAGNETIC RESONANCE; STEADY STATE; SURFACE PLASMON RESONANCE; THERMOSTABILITY; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CHEMISTRY; DNA METHYLATION; DRUG DEVELOPMENT; ESCHERICHIA COLI; GENE EXPRESSION REGULATION; GENETICS; NEOPLASMS; PATHOLOGY; PROTEIN CONFORMATION; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ALLOSTERIC SITE; CRYSTALLOGRAPHY, X-RAY; DNA METHYLATION; DRUG DISCOVERY; ENZYME INHIBITORS; ESCHERICHIA COLI; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; ISOCITRATE DEHYDROGENASE; MAGNESIUM; MUTANT PROTEINS; NEOPLASMS; PROTEIN CONFORMATION;

EID: 84920973012     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.608497     Document Type: Article

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