dc.contributor.author | Couty, S | |
dc.contributor.author | Westwood, IM | |
dc.contributor.author | Kalusa, A | |
dc.contributor.author | Cano, C | |
dc.contributor.author | Travers, J | |
dc.contributor.author | Boxall, K | |
dc.contributor.author | Chow, CL | |
dc.contributor.author | Burns, S | |
dc.contributor.author | Schmitt, J | |
dc.contributor.author | Pickard, L | |
dc.contributor.author | Barillari, C | |
dc.contributor.author | McAndrew, PC | |
dc.contributor.author | Clarke, PA | |
dc.contributor.author | Linardopoulos, S | |
dc.contributor.author | Griffin, RJ | |
dc.contributor.author | Aherne, GW | |
dc.contributor.author | Raynaud, FI | |
dc.contributor.author | Workman, P | |
dc.contributor.author | Jones, K | |
dc.contributor.author | van Montfort, RLM | |
dc.date.accessioned | 2018-05-24T10:20:26Z | |
dc.date.issued | 2013-08-25 | |
dc.identifier.citation | Oncotarget, 2013, 4 (10), pp. 1647 - 1661 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1688 | |
dc.identifier.eissn | 1949-2553 | |
dc.identifier.doi | 10.18632/oncotarget.1255 | |
dc.description.abstract | The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we describe the identification of three series of chemically distinct S6K1 inhibitors. In addition, we report a novel PKA-S6K1 chimeric protein with five mutations in or near its ATP-binding site, which was used to determine the binding mode of two of the three inhibitor series, and provided a robust system to aid the optimisation of the oxadiazole-substituted benzimidazole inhibitor series. We show that the resulting oxadiazole-substituted aza-benzimidazole is a potent and ligand efficient S6 kinase inhibitor, which blocks the phosphorylation of RPS6 at Ser235/236 in TSC negative HCV29 human bladder cancer cells by inhibiting S6 kinase activity and thus provides a useful tool compound to investigate the function of S6 kinases. | |
dc.format | Print | |
dc.format.extent | 1647 - 1661 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | IMPACT JOURNALS LLC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Imidazoles | |
dc.subject | Cyclic AMP-Dependent Protein Kinases | |
dc.subject | Ribosomal Protein S6 Kinases, 90-kDa | |
dc.subject | Recombinant Fusion Proteins | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Signal Transduction | |
dc.subject | Structure-Activity Relationship | |
dc.subject | Phosphorylation | |
dc.subject | Drug Design | |
dc.subject | Models, Molecular | |
dc.subject | Urinary Bladder Neoplasms | |
dc.subject | High-Throughput Screening Assays | |
dc.title | The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.18632/oncotarget.1255 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2013-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Oncotarget | |
pubs.issue | 10 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Drug Target Discovery | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Hit Discovery & Structural Design | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3 | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Structure-Based Drug Design | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structure-Based Drug Design | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Drug Target Discovery | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Hit Discovery & Structural Design | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3 | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Structure-Based Drug Design | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structure-Based Drug Design | |
pubs.publication-status | Published | |
pubs.volume | 4 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Drug Target Discovery | |
icr.researchteam | Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group) | |
icr.researchteam | Medicinal Chemistry 3 | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
icr.researchteam | Hit Discovery & Structural Design | |
icr.researchteam | Structure-Based Drug Design | |
dc.contributor.icrauthor | Westwood, Isaac | |
dc.contributor.icrauthor | Schmitt, Jessica Andrea | |
dc.contributor.icrauthor | Clarke, Paul | |
dc.contributor.icrauthor | Linardopoulos, Spyridon | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Workman, Paul | |
dc.contributor.icrauthor | Jones, Keith | |
dc.contributor.icrauthor | Van Montfort, Robert | |