dc.contributor.author | Davis, OA | |
dc.contributor.author | Cheung, K-MJ | |
dc.contributor.author | Brennan, A | |
dc.contributor.author | Lloyd, MG | |
dc.contributor.author | Rodrigues, MJ | |
dc.contributor.author | Pierrat, OA | |
dc.contributor.author | Collie, GW | |
dc.contributor.author | Le Bihan, Y-V | |
dc.contributor.author | Huckvale, R | |
dc.contributor.author | Harnden, AC | |
dc.contributor.author | Varela, A | |
dc.contributor.author | Bright, MD | |
dc.contributor.author | Eve, P | |
dc.contributor.author | Hayes, A | |
dc.contributor.author | Henley, AT | |
dc.contributor.author | Carter, MD | |
dc.contributor.author | McAndrew, PC | |
dc.contributor.author | Talbot, R | |
dc.contributor.author | Burke, R | |
dc.contributor.author | van Montfort, RLM | |
dc.contributor.author | Raynaud, FI | |
dc.contributor.author | Rossanese, OW | |
dc.contributor.author | Meniconi, M | |
dc.contributor.author | Bellenie, BR | |
dc.contributor.author | Hoelder, S | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-08-23T11:31:26Z | |
dc.date.available | 2022-08-23T11:31:26Z | |
dc.date.issued | 2022-06-23 | |
dc.identifier.citation | Journal of Medicinal Chemistry, 2022, 65 (12), pp. 8169 - 8190 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5313 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.doi | 10.1021/acs.jmedchem.1c02174 | |
dc.description.abstract | To identify new chemical series with enhanced binding affinity to the BTB domain of B-cell lymphoma 6 protein, we targeted a subpocket adjacent to Val18. With no opportunities for strong polar interactions, we focused on attaining close shape complementarity by ring fusion onto our quinolinone lead series. Following exploration of different sized rings, we identified a conformationally restricted core which optimally filled the available space, leading to potent BCL6 inhibitors. Through X-ray structure-guided design, combined with efficient synthetic chemistry to make the resulting novel core structures, a >300-fold improvement in activity was obtained by the addition of seven heavy atoms. | |
dc.format | Print-Electronic | |
dc.format.extent | 8169 - 8190 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER CHEMICAL SOC | |
dc.relation.ispartof | Journal of Medicinal Chemistry | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | BTB-POZ Domain | |
dc.subject | Protein Binding | |
dc.subject | Proto-Oncogene Proteins c-bcl-6 | |
dc.title | Optimizing Shape Complementarity Enables the Discovery of Potent Tricyclic BCL6 Inhibitors. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-12-01 | |
dc.date.updated | 2022-08-23T11:30:23Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1021/acs.jmedchem.1c02174 | |
rioxxterms.licenseref.startdate | 2022-06-23 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35657291 | |
pubs.issue | 12 | |
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/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 4 (including Analytical Chemistry) | |
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.publication-status | Published | |
pubs.volume | 65 | |
icr.researchteam | Hit Discov Struct Design | |
icr.researchteam | Clinical Pharma & Trials | |
icr.researchteam | Directorate Canc Ther | |
icr.researchteam | Medicinal Chemistry 4 | |
dc.contributor.icrauthor | Pierrat, Olivier | |
dc.contributor.icrauthor | Talbot, Rachel | |
dc.contributor.icrauthor | Burke, Rosemary | |
dc.contributor.icrauthor | Van Montfort, Robert | |
dc.contributor.icrauthor | Raynaud, Florence | |
dc.contributor.icrauthor | Rossanese, Olivia | |
dc.contributor.icrauthor | Hoelder, Swen | |
icr.provenance | Deposited by Mr Arek Surman on 2022-08-23. Deposit type is initial. No. of files: 1. Files: Optimizing Shape Complementarity Enables the Discovery of Potent Tricyclic BCL6 Inhibitors.pdf | |