Sökning: onr:"swepub:oai:DiVA.org:uu-279559" > Aurora kinase inhib...
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000 | 06546naa a2200661 4500 | |
001 | oai:DiVA.org:uu-279559 | |
003 | SwePub | |
008 | 160302s2016 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2795592 URI |
024 | 7 | a https://doi.org/10.1126/scitranslmed.aad23552 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Ashton, Susanu AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
245 | 1 0 | a Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo |
264 | 1 | b American Association for the Advancement of Science (AAAS),c 2016 |
338 | a print2 rdacarrier | |
520 | a Efforts to apply nanotechnology in cancer have focused almost exclusively on the delivery of cytotoxic drugs to improve therapeutic index. There has been little consideration of molecularly targeted agents, in particular kinase inhibitors, which can also present considerable therapeutic index limitations. We describe the development of Accurin polymeric nanoparticles that encapsulate the clinical candidate AZD2811, an Aurora B kinase inhibitor, using an ion pairing approach. Accurins increase biodistribution to tumor sites and provide extended release of encapsulated drug payloads. AZD2811 nanoparticles containing pharmaceutically acceptable organic acids as ion pairing agents displayed continuous drug release for more than 1 week in vitro and a corresponding extended pharmacodynamic reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration. A specific AZD2811 nanoparticle formulation profile showed accumulation and retention in tumors with minimal impact on bone marrow pathology, and resulted in lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of AZD1152, a water-soluble prodrug of AZD2811. These studies demonstrate that AZD2811 can be formulated in nanoparticles using ion pairing agents to give improved efficacy and tolerability in preclinical models with less frequent dosing. Accurins specifically, and nanotechnology in general, can increase the therapeutic index of molecularly targeted agents, including kinase inhibitors targeting cell cycle and oncogenic signal transduction pathways, which have to date proved toxic in humans. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng |
700 | 1 | a Song, Young Hou BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 aut |
700 | 1 | a Nolan, Jimu BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 aut |
700 | 1 | a Cadogan, Elaineu AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Murray, Jimu AstraZeneca, Pharmaceut Dev, Macclesfield SK10 2NX, Cheshire, England.4 aut |
700 | 1 | a Odedra, Rajeshu AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Foster, Johnu AstraZeneca R&D, Drug Safety & Metab, Innovat Med, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Hall, Peter A.u AstraZeneca R&D, Drug Safety & Metab, Innovat Med, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Low, Susanu BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 aut |
700 | 1 | a Taylor, Paulau AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Ellston, Rebeccau AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Polanska, Urszula M.u AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Wilson, Joanneu AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Howes, Colinu AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Smith, Aaronu AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Goodwin, Richard J. A.u AstraZeneca R&D, Drug Safety & Metab, Innovat Med, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Swales, John G.u AstraZeneca R&D, Drug Safety & Metab, Innovat Med, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Strittmatter, Nicoleu Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England.4 aut |
700 | 1 | a Takats, Zoltanu Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England.4 aut |
700 | 1 | a Nilsson, Annau Uppsala universitet,Institutionen för farmaceutisk biovetenskap4 aut0 (Swepub:uu)annil134 |
700 | 1 | a Andrén, Peru Uppsala universitet,Institutionen för farmaceutisk biovetenskap4 aut0 (Swepub:uu)perandre |
700 | 1 | a Trueman, Dawnu AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Walker, Mikeu AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Reimer, Corinne L.u AstraZeneca, Oncol iMED, Gatehouse Pk, Boston, MA 02451 USA.4 aut |
700 | 1 | a Troiano, Gregu BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 aut |
700 | 1 | a Parsons, Donaldu BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 aut |
700 | 1 | a De Witt, Davidu BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 aut |
700 | 1 | a Ashford, Marianneu AstraZeneca, Pharmaceut Dev, Macclesfield SK10 2NX, Cheshire, England.4 aut |
700 | 1 | a Hrkach, Jeffu BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 aut |
700 | 1 | a Zale, Stephenu BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 aut |
700 | 1 | a Jewsbury, Philip J.u AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
700 | 1 | a Barry, Simon T.u AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.4 aut |
710 | 2 | a AstraZeneca, Oncol iMED, Macclesfield SK10 4TG, Cheshire, England.b BIND Therapeut, 325 Vassar St, Cambridge, MA 02139 USA.4 org |
773 | 0 | t Science Translational Medicined : American Association for the Advancement of Science (AAAS)g 8:325q 8:325x 1946-6234x 1946-6242 |
856 | 4 | u http://hdl.handle.net/10044/1/37595 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-279559 |
856 | 4 8 | u https://doi.org/10.1126/scitranslmed.aad2355 |
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