dc.contributor.author | Guillard, S | |
dc.contributor.author | Kolasinska-Zwierz, P | |
dc.contributor.author | Debreczeni, J | |
dc.contributor.author | Breed, J | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Bery, N | |
dc.contributor.author | Marwood, R | |
dc.contributor.author | Tart, J | |
dc.contributor.author | Overman, R | |
dc.contributor.author | Stocki, P | |
dc.contributor.author | Mistry, B | |
dc.contributor.author | Phillips, C | |
dc.contributor.author | Rabbitts, T | |
dc.contributor.author | Jackson, R | |
dc.contributor.author | Minter, R | |
dc.date.accessioned | 2020-12-21T14:07:14Z | |
dc.date.issued | 2017-07-14 | |
dc.identifier.citation | Nature communications, 2017, 8 pp. 16111 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4263 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/ncomms16111 | |
dc.description.abstract | Ras mutations are the oncogenic drivers of many human cancers and yet there are still no approved Ras-targeted cancer therapies. Inhibition of Ras nucleotide exchange is a promising new approach but better understanding of this mechanism of action is needed. Here we describe an antibody mimetic, DARPin K27, which inhibits nucleotide exchange of Ras. K27 binds preferentially to the inactive Ras GDP form with a Kd of 4 nM and structural studies support its selectivity for inactive Ras. Intracellular expression of K27 significantly reduces the amount of active Ras, inhibits downstream signalling, in particular the levels of phosphorylated ERK, and slows the growth in soft agar of HCT116 cells. K27 is a potent, non-covalent inhibitor of nucleotide exchange, showing consistent effects across different isoforms of Ras, including wild-type and oncogenic mutant forms. | |
dc.format | Electronic | |
dc.format.extent | 16111 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | HCT116 Cells | |
dc.subject | Humans | |
dc.subject | ras Proteins | |
dc.subject | Antibodies | |
dc.subject | Cell Proliferation | |
dc.subject | Molecular Structure | |
dc.subject | Ankyrin Repeat | |
dc.subject | Drug Design | |
dc.subject | HEK293 Cells | |
dc.subject | Molecular Targeted Therapy | |
dc.title | Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-05-30 | |
rioxxterms.versionofrecord | 10.1038/ncomms16111 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-07-14 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
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/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Chromosomal Translocations and Intracellular Antibody Therapeutics | |
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/Chromosomal Translocations and Intracellular Antibody Therapeutics | |
pubs.publication-status | Published | |
pubs.volume | 8 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Chromosomal Translocations and Intracellular Antibody Therapeutics | |
dc.contributor.icrauthor | Rabbitts, Terence | |