Publication:
Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs.

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dc.contributor.authorWilbs, Jonas
dc.contributor.authorKong, Xu-Dong
dc.contributor.authorMiddendorp, Simon J
dc.contributor.authorPrince, Raja
dc.contributor.authorCooke, Alida
dc.contributor.authorDemarest, Caitlin T
dc.contributor.authorAbd El Hafez, Mai Moustafa Ahmed
dc.contributor.authorRoberts, Kalliope
dc.contributor.authorUmei, Nao
dc.contributor.authorGonschorek, Patrick
dc.contributor.authorLamers, Christina
dc.contributor.authorDeyle, Kaycie
dc.contributor.authorRieben, Robert
dc.contributor.authorCook, Keith E
dc.contributor.authorAngelillo, Anne
dc.contributor.authorHeinis, Christian
dc.date.accessioned2024-09-20T09:08:41Z
dc.date.available2024-09-20T09:08:41Z
dc.date.issued2020-08-04
dc.description.abstractInhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knock-out or inhibition in animals reduced thrombosis without causing abnormal bleeding. Herein, we have engineered a macrocyclic peptide inhibitor of activated FXII (FXIIa) with sub-nanomolar activity (Ki = 370 ± 40 pM) and a high stability (t1/2 > 5 days in plasma), allowing for the preclinical evaluation of a first synthetic FXIIa inhibitor. This 1899 Da molecule, termed FXII900, efficiently blocks FXIIa in mice, rabbits, and pigs. We found that it reduces ferric-chloride-induced experimental thrombosis in mice and suppresses blood coagulation in an extracorporeal membrane oxygenation (ECMO) setting in rabbits, all without increasing the bleeding risk. This shows that FXIIa activity is controllable in vivo with a synthetic inhibitor, and that the inhibitor FXII900 is a promising candidate for safe thromboprotection in acute medical conditions.
dc.description.sponsorshipDepartment for BioMedical Research, Forschungsbereich Murtenstrasse 50
dc.description.sponsorshipDepartment for BioMedical Research (DBMR)
dc.description.sponsorshipDepartment for BioMedical Research, Forschungsgruppe Hämatologie (Erwachsene)
dc.identifier.doi10.7892/boris.145764
dc.identifier.pmid32753636
dc.identifier.publisherDOI10.1038/s41467-020-17648-w
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/44954
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.ispartofNature communications
dc.relation.issn2041-1723
dc.relation.organizationDCD5A442BD18E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C26FE17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C39CE17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C5F4E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C055E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C2CBE17DE0405C82790C4DE2
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.titleCyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs.
dc.typearticle
dspace.entity.typePublication
oaire.citation.issue1
oaire.citation.startPage3890
oaire.citation.volume11
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oairecerif.author.affiliationDepartment for BioMedical Research, Forschungsbereich Murtenstrasse 50
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oairecerif.author.affiliationDepartment for BioMedical Research (DBMR)
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oairecerif.author.affiliationDepartment for BioMedical Research, Forschungsgruppe Hämatologie (Erwachsene)
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oairecerif.author.affiliation2Department for BioMedical Research, Forschungsgruppe Herz und Gefässe
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oairecerif.author.affiliation2Department for BioMedical Research, Forschungsgruppe Herz und Gefässe
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oairecerif.author.affiliation2Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor
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unibe.date.licenseChanged2020-08-11 12:38:36
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unibe.eprints.legacyId145764
unibe.journal.abbrevTitleNAT COMMUN
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