title: Bothrojaracin, a Bothrops jararaca snake venom-derived (pro)thrombin inhibitor, as an anti-thrombotic molecule.
abstract: Bothrojaracin (BJC) is a selective and potent thrombin inhibitor (KD = 0.6 nM) which also binds to prothrombin on proexosite I (KD = 175 nM). Incubation of BJC with human or rat plasma produced a band that co-migrates with purified prothrombin-BJC complex. We further analyzed the in vivo anti-thrombotic effect of BJC on a venous thrombosis model in rats that combines stasis and hypercoagulability. The administration of 1 mg/kg (i.v.) doses of BJC decreased thrombus weight by approximately 95%. Evaluation of the in vivo effect of BJC in mice using a pulmonary thromboembolism model induced by thrombin showed that BJC protects 100% of mice from death. Altogether, our data show that BJC is a potent anti-thrombotic agent that could further help the development of new prothrombin-directed drugs.
authors.affiliation: Instituto de Bioquímica Médica, CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. lzingali@bioqmed.ufrj.br
authors.forename: Russolina B
authors.initials: RB
authors.lastname: Zingali
authors.forename: Marcos S
authors.initials: MS
authors.lastname: Ferreira
authors.forename: Mariane
authors.initials: M
authors.lastname: Assafim
authors.forename: Flávia S
authors.initials: FS
authors.lastname: Frattani
authors.forename: Robson Q
authors.initials: RQ
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D003435:Crotalid Venoms / Q000627:therapeutic use*; D006801:Humans; D051189:Murinae; D012910:Snake Venoms / Q000627:therapeutic use; D013917:Thrombin / Q000037:antagonists & inhibitors*; D020246:Venous Thrombosis / Q000188:drug therapy
chemical_list: D003435:Crotalid Venoms; D012910:Snake Venoms; C083739:bothrojaracin; D013917:Thrombin