This HTML5 document contains 51 embedded RDF statements represented using HTML+Microdata notation.

The embedded RDF content will be recognized by any processor of HTML5 Microdata.

Namespace Prefixes

PrefixIRI
dctermshttp://purl.org/dc/terms/
n7http://localhost/temp/predkladatel/
n15http://linked.opendata.cz/resource/domain/vavai/riv/tvurce/
n14http://linked.opendata.cz/ontology/domain/vavai/
shttp://schema.org/
skoshttp://www.w3.org/2004/02/skos/core#
n3http://linked.opendata.cz/ontology/domain/vavai/riv/
n6http://linked.opendata.cz/resource/domain/vavai/vysledek/RIV%2F00216224%3A14310%2F08%3A00035899%21RIV10-MSM-14310___/
n2http://linked.opendata.cz/resource/domain/vavai/vysledek/
rdfhttp://www.w3.org/1999/02/22-rdf-syntax-ns#
n12http://linked.opendata.cz/ontology/domain/vavai/riv/klicoveSlovo/
n17http://linked.opendata.cz/ontology/domain/vavai/riv/duvernostUdaju/
xsdhhttp://www.w3.org/2001/XMLSchema#
n8http://linked.opendata.cz/ontology/domain/vavai/riv/jazykVysledku/
n4http://linked.opendata.cz/ontology/domain/vavai/riv/aktivita/
n13http://linked.opendata.cz/ontology/domain/vavai/riv/obor/
n9http://linked.opendata.cz/ontology/domain/vavai/riv/druhVysledku/
n16http://reference.data.gov.uk/id/gregorian-year/

Statements

Subject Item
n2:RIV%2F00216224%3A14310%2F08%3A00035899%21RIV10-MSM-14310___
rdf:type
skos:Concept n14:Vysledek
dcterms:description
CDK2 inhibitors containing the related bicyclic heterocycles pyrazolopyrimidines and imidazopyrazines were discovered through high-throughput screening. Crystal structures of inhibitors with these bicyclic cores and two more related ones show that all but one have a common binding mode featuring two hydrogen bonds (H-bonds) to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would bind more tightly to the hinge, pyrazolopyrimidines gain an advantage in potency through participation of N4 in an H-bond network involving two catalytic residues and bridging water molecules. Further insight into inhibitor/CDK2 interactions was gained from analysis of additional crystal structures. Significant gains in potency were obtained by optimizing the fit of hydrophobic substituents to the gatekeeper region of the ATP binding site. The most potent inhibitors have good selectivity. CDK2 inhibitors containing the related bicyclic heterocycles pyrazolopyrimidines and imidazopyrazines were discovered through high-throughput screening. Crystal structures of inhibitors with these bicyclic cores and two more related ones show that all but one have a common binding mode featuring two hydrogen bonds (H-bonds) to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would bind more tightly to the hinge, pyrazolopyrimidines gain an advantage in potency through participation of N4 in an H-bond network involving two catalytic residues and bridging water molecules. Further insight into inhibitor/CDK2 interactions was gained from analysis of additional crystal structures. Significant gains in potency were obtained by optimizing the fit of hydrophobic substituents to the gatekeeper region of the ATP binding site. The most potent inhibitors have good selectivity.
dcterms:title
Structure-guided discovery of cyclin-dependent kinase inhibitors Structure-guided discovery of cyclin-dependent kinase inhibitors
skos:prefLabel
Structure-guided discovery of cyclin-dependent kinase inhibitors Structure-guided discovery of cyclin-dependent kinase inhibitors
skos:notation
RIV/00216224:14310/08:00035899!RIV10-MSM-14310___
n3:aktivita
n4:N
n3:aktivity
N
n3:cisloPeriodika
89
n3:dodaniDat
n16:2010
n3:domaciTvurceVysledku
n15:1390333
n3:druhVysledku
n9:J
n3:duvernostUdaju
n17:S
n3:entitaPredkladatele
n6:predkladatel
n3:idSjednocenehoVysledku
397862
n3:idVysledku
RIV/00216224:14310/08:00035899
n3:jazykVysledku
n8:eng
n3:klicovaSlova
CDK2; kinase; inhibitor
n3:klicoveSlovo
n12:CDK2 n12:inhibitor n12:kinase
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[AA2C312E2DC6]
n3:nazevZdroje
Biopolymers
n3:obor
n13:CC
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
15
n3:rokUplatneniVysledku
n16:2008
n3:svazekPeriodika
2008
n3:tvurceVysledku
Le, Hung Parry, David Windsor, William Mayhood, Todd Duca, Jose Ramanathan, Lata Hruza, Alan Doll, Ronald Paruch, Kamil Seghezzi, Wolfgang Lees, Emma Guzi, Timothy Madison, Vincent Fischmann, Thierry Dwyer, Michael
n3:wos
000254569700008
s:issn
0006-3525
s:numberOfPages
8
n7:organizacniJednotka
14310