Discovery of Potent and Selective RSK Inhibitors as Biological Probes

Journal of Medicinal Chemistry

Volumn 58, Issue 17, 2015, Pages 6766-6783

  Jain, Rama ^a   Mathur, Michelle ^a   Lan, Jiong ^a   Costales, Abran ^a   Atallah, Gordana ^a   Ramurthy, Savithri ^a   Subramanian, Sharadha ^a   Setti, Lina ^a   Feucht, Paul ^a   Warne, Bob ^a   Doyle, Laura ^a   Basham, Stephen ^a   Jefferson, Anne B ^a   Lindvall, Mika ^a   Appleton, Brent A ^a   Shafer, Cynthia M ^a  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,6 DICHLORO 4 [4 (4 FLUOROPHENYL)PYRIDIN 3 YL] PHENOL; 2,6 DIFLUORO 4 (4 ISOPROPYLPYRIDIN 3 YL)PHENOL; 2,6 DIFLUORO 4 (4 PHENYLPYRIDIN 3 YL)PHENOL; 2,6 DIFLUORO 4 (4 [TETRAHYDRO 2H PYRAN 4 YL) PYRIDIN 3 YL )PHENOL; 2,6 DIFLUORO 4 (6 METHOXY [3,4' BIPYRIDIN] 3' YL)PHENOL; 2,6 DIFLUORO 4 [4 (3 METHOXYPHENYL)PYRIDIN 3YL]PHENOL; 2,6 DIFLUORO 4 [4 (3 MORPHOLINOPHENYL)PYRIDIN 3 YL]; 2,6 DIFLUORO 4 [4 (4 FLUOROPHENYL)PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 (4 HYDROXYPHENYL) 1H PYRAZOL 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 (4 HYDROXYPHENYL)PYRIDIN 3YL]PHENOL; 2,6 DIFLUORO 4 [4 (4 METHOPHENYL)PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 (4 MORPHOLINOPHENYL)PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 (M TOLYL)PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 (P TOTYL)PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 (PIPERIDIN 4 YL)PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 [3 (4 METHYLPIPERAZIN 1 YL)PHENYL]PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 [4 (4 METHYLPIPERAZIN 1 YL) PHENYL]PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 [4 (METHYLPIPERAZIN 1 YL)PHENYL]PYRIDIN 3 YL]PHENOL; 2,6 DIFLUORO 4 [4 [4 (PIPERAZIN 1 YL)PHENYL]PYRIDIN 3 YL]PHENOL; 4 (3 PHENYL 1H PYRAZOL 4 YL)PHENOL; 4 (4 PHENYL 1H PYRAZOL 3 YL)PHENOL; 4 (5 AMINO 4 PHENYL 1H PYRAZOL 3 YL)PHENOL; 4 [3 (3,5 DIFLUORO 4 HYDROXYPHENYL)PYRIDIN 4YL] N METHYLBENZAMIDE; 4 [4 [3 (1H PYRAZOL 4 YL)PHENYL]PYRIDIN 3 YL] 2,6 DIFLUOROPHENOL; 4 [4 [3 (2 AMINOETHOXY)PHENYL]PYRIDIN 3 YL] 2,6 DIFLUOROPHENOL; 4 [6 AMINO 4 [4 (4 METHYLPIPERAZIN 1 YL)PHENYL]PYRIDIN 3 YL] 2,6 DIFLUOROPHENOL; 4,4' (PYRIDINE 3,4 DIYL)DIPHENOL; PROTEIN KINASE INHIBITOR; PROTEIN P90; UNCLASSIFIED DRUG; UNINDEXED DRUG; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; S6 KINASE; Y BOX BINDING PROTEIN 1;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DRUG DESIGN; DRUG SYNTHESIS; ENANTIOMER; HYDROGEN BOND; IN VITRO STUDY; IN VIVO STUDY; MALE; NONHUMAN; PHARMACOPHORE; PLASMA HALF LIFE; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; SUZUKI REACTION; VOLUME OF DISTRIBUTION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; HUMAN; METABOLISM; MOUSE; PHOSPHORYLATION; PROTEIN CONFORMATION; SIGNAL TRANSDUCTION; SPRAGUE DAWLEY RAT; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ANIMALS; CELL LINE; CRYSTALLOGRAPHY, X-RAY; HUMANS; MALE; MICE; MODELS, MOLECULAR; PHOSPHORYLATION; PROTEIN CONFORMATION; PYRAZOLES; PYRIDINES; PYRIMIDINES; RATS, SPRAGUE-DAWLEY; RIBOSOMAL PROTEIN S6 KINASES, 90-KDA; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; Y-BOX-BINDING PROTEIN 1;

EID: 84941558956     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00450     Document Type: Article

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25. A full listing of the KinomeScan for 46 and 47 is included in the Supporting Information in ref 15. The pan RSK KinomeScan data for 47 are RSK1 0%, RSK2 0%, RSK3 0.05%, and RSK4 0% of control at 10 μM. KinomeScan data are reported as 100-(% control); thus, smaller numbers indicate stronger binders. The information regarding the KinomeScan assays can be found at http://www.discoverx.com/technologies-platforms/competitive-binding-technology/kinomescan-technology-platform/kinomescan-assay-process.