Analysis of kinase inhibitor selectivity using a thermodynamics-based partition index

Journal of Medicinal Chemistry

Volumn 53, Issue 11, 2010, Pages 4502-4510

  Cheng, Alan C ^a   Eksterowicz, John ^a   Geuns Meyer, Stephanie ^a   Sun, Yaxiong ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [4 (3 AMINO 1H INDAZOL 4 YL)PHENYL] 3 (2 FLUORO 5 METHYLPHENYL)UREA; 2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 2 [[3 [4 [5 [2 (3 FLUOROANILINO) 2 OXOETHYL] 1H PYRAZOL 3 YLAMINO] 7 QUINAZOLINYLOXY]PROPYL](ETHYL)AMINO]ETHYL DIHYDROGEN PHOSPHATE; 4 (4 FLUOROPHENYL) 2 (4 HYDROXYPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 [4 (1,3 BENZODIOXOL 5 YL) 5 (2 PYRIDINYL) 1H IMIDAZOL 2 YL]BENZAMIDE; 4 [[9 CHLORO 7 (2,6 DIFLUOROPHENYL) 5H PYRIMIDO[5,4 D][2]BENZAZEPIN 2 YL]AMINO]BENZOIC ACID; 4 [N [1 (2 CYANO 1 OXOETHYL) 4 METHYL 3 PIPERIDINYL] N METHYLAMINO]PYRROLO[2,3 D]PYRIMIDINE; 5 (2,6 DICHLOROPHENYL) 2 (2,4 DIFLUOROPHENYLTHIO)PYRIMIDO[1,6 B]PYRIDAZIN 6 ONE; CANERTINIB; CHIR 265; CP 724714; DORAMAPIMOD; DOVITINIB; ERLOTINIB; GEFITINIB; GW 2580; IMATINIB; LAPATINIB; MOTESANIB; N [5 (5 TERT BUTYL 2 OXAZOLYLMETHYLTHIO) 2 THIAZOLYL]ISONIPECOTAMIDE; PAZOPANIB; PELITINIB; PROTEIN TYROSINE KINASE INHIBITOR; ROSCOVITINE; RUBOXISTAURIN; SORAFENIB; TANDUTINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; VATALANIB;

ARTICLE; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; HUMAN; LIGAND BINDING; PROTEIN BINDING; STRUCTURE ACTIVITY RELATION; THERMODYNAMICS;

DRUG EVALUATION, PRECLINICAL; INHIBITORY CONCENTRATION 50; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; SUBSTRATE SPECIFICITY; THERMODYNAMICS;

EID: 77953193637     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100301x     Document Type: Article

References (24)

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23. This is due to normalization of the cumulative inhibition values in the Gini procedureî-̧see ref 9 for details. A very selective compound will have a low cumulative inhibition value relative to a less selective compound. The cumulative inhibition values are normalized to the same value of one. The resulting effect is that with very selective compounds, low POC values end up being scaled up to achieve normalization, and small differences (e.g., 99 POC versus 97 POC) are magnified.
24. Caliper ProfilerPro Assay Kits 1 and 2 from Caliper Life Sciences, Hopkinton, MA. Assays performed in 2008.