Milvexian, an orally bioavailable, small-molecule, reversible, direct inhibitor of factor XIa: In vitro studies and in vivo evaluation in experimental thrombosis in rabbits.

ABSTRACT:

Background

Milvexian (BMS-986177/JNJ-70033093) is an orally bioavailable factor XIa (FXIa) inhibitor currently in phase 2 clinical trials.

Objectives

To evaluate in vitro properties and in vivo characteristics of milvexian.

Methods

In vitro properties of milvexian were evaluated with coagulation and enzyme assays, and in vivo profiles were characterized with rabbit models of electrolytic-induced carotid arterial thrombosis and cuticle bleeding time (BT).

Results

Milvexian is an active-site, reversible inhibitor of human and rabbit FXIa (K_i 0.11 and 0.38 nM, respectively). Milvexian increased activated partial thromboplastin time (APTT) without changing prothrombin time and potently prolonged plasma APTT in humans and rabbits. Milvexian did not alter

SUBMITTER: Wong PC 

PROVIDER: S-EPMC9299130 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature