| http://purl.uniprot.org/citations/20072125 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20072125 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20072125 | http://www.w3.org/2000/01/rdf-schema#comment | "In an effort to find new pharmacological modalities to overcome resistance to ATP-binding-site inhibitors of Bcr-Abl, we recently reported the discovery of GNF-2, a selective allosteric Bcr-Abl inhibitor. Here, using solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry, we show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, when used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr-Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model. These results show that therapeutically relevant inhibition of Bcr-Abl activity can be achieved with inhibitors that bind to the myristate-binding site and that combining allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature08675"xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature08675"xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Daley G.Q."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Daley G.Q."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Deng X."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Deng X."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Liu G."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Liu G."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Jahnke W."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Jahnke W."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Sun F."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Sun F."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Choi Y."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Choi Y."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Azam M."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Azam M."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Strauss A."xsd:string |
| http://purl.uniprot.org/citations/20072125 | http://purl.uniprot.org/core/author | "Strauss A."xsd:string |