Discovery of Milvexian, a High-Affinity, Orally Bioavailable Inhibitor of Factor XIa in Clinical Studies for Antithrombotic Therapy.

Animals Mice Rabbits Administration, Oral Carotid Artery Thrombosis / drug therapy Factor XIa / antagonists & inhibitors Fibrinolytic Agents / administration & dosage Macaca fascicularis Molecular Structure Pyrazoles / administration & dosage Pyrimidines / administration & dosage Rats, Sprague-Dawley Structure-Activity Relationship Triazoles / administration & dosage

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
10 02 2022
Historique:
pubmed: 9 9 2021
medline: 23 2 2022
entrez: 8 9 2021
Statut: ppublish

Résumé

Factor XIa (FXIa) is an enzyme in the coagulation cascade thought to amplify thrombin generation but has a limited role in hemostasis. From preclinical models and human genetics, an inhibitor of FXIa has the potential to be an antithrombotic agent with superior efficacy and safety. Reversible and irreversible inhibitors of FXIa have demonstrated excellent antithrombotic efficacy without increased bleeding time in animal models (Weitz, J. I., Chan, N. C.

Identifiants

DOI: 10.1021/acs.jmedchem.1c00613 PMID: 34494428
pubmed: 34494428
doi: 10.1021/acs.jmedchem.1c00613
doi:

Substances chimiques

Factor XIa EC 3.4.21.27
Fibrinolytic Agents 0
milvexian 0W79NDQ608
Pyrazoles 0
Pyrimidines 0
Triazoles 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1770-1785

Auteurs

Andrew K Dilger (AK)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Kumar B Pabbisetty (KB)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.
ORCID: 0000-0001-9669-4059

James R Corte (JR)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.
ORCID: 0000-0002-4790-597X

Indawati De Lucca (I)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Tianan Fang (T)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Wu Yang (W)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Donald J P Pinto (DJP)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.
ORCID: 0000-0003-4356-5979

Yufeng Wang (Y)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Yeheng Zhu (Y)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Arvind Mathur (A)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Jianqing Li (J)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.
ORCID: 0000-0002-8445-9796

Xiaoping Hou (X)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.
ORCID: 0000-0001-6169-3443

Daniel Smith (D)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Dawn Sun (D)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Huiping Zhang (H)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Subramaniam Krishnananthan (S)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Dauh-Rurng Wu (DR)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Joseph E Myers (JE)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Steven Sheriff (S)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Karen A Rossi (KA)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Silvi Chacko (S)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Joanna J Zheng (JJ)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Michael A Galella (MA)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Theresa Ziemba (T)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Elizabeth A Dierks (EA)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Jeffrey M Bozarth (JM)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Yiming Wu (Y)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Earl Crain (E)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Pancras C Wong (PC)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Joseph M Luettgen (JM)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

Ruth R Wexler (RR)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.

William R Ewing (WR)

Research and Development, Bristol Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey 08543, United States.
ORCID: 0000-0002-9434-8053

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Lagomorpha › Lapins › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie orale › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thromboembolie › Embolie et thrombose intracrâniennes › Thrombose carotidienne › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Facteur XI › Facteur XIa › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents hématologiques › Fibrinolytiques › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca › Macaca fascicularis › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Pyrazoles › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Discovery of Milvexian, a High-Affinity,...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Triazoles › Discovery of Milvexian, a High-Affinity,...