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Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs.
Blood ; 118(3): 757-65, 2011 Jul 21.
Article em En | MEDLINE | ID: mdl-21576702
Neutralizing the interaction of the platelet receptor gpIb with VWF is an attractive strategy to treat and prevent thrombotic complications. ALX-0081 is a bivalent Nanobody which specifically targets the gpIb-binding site of VWF and interacts avidly with VWF. Nanobodies are therapeutic proteins derived from naturally occurring heavy-chain-only Abs and combine a small molecular size with a high inherent stability. ALX-0081 exerts potent activity in vitro and in vivo. Perfusion experiments with blood from patients with acute coronary syndrome on standard antithrombotics demonstrated complete inhibition of platelet adhesion after addition of ALX-0081, while in the absence of ALX-0081 residual adhesion was observed. In a baboon efficacy and safety model measuring acute thrombosis and surgical bleeding, ALX-0081 showed a superior therapeutic window compared with marketed antithrombotics. Pharmacokinetic and biodistribution experiments demonstrated target-mediated clearance of ALX-0081, which leads to a self-regulating disposition behavior. In conclusion, these preclinical data demonstrate that ALX-0081 combines a high efficacy with an improved safety profile compared with currently marketed antithrombotics. ALX-0081 has entered clinical development.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trombose / Inibidores da Agregação Plaquetária / Cadeias Pesadas de Imunoglobulinas / Anticorpos Biespecíficos / Anticorpos de Cadeia Única / Fibrinolíticos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trombose / Inibidores da Agregação Plaquetária / Cadeias Pesadas de Imunoglobulinas / Anticorpos Biespecíficos / Anticorpos de Cadeia Única / Fibrinolíticos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2011 Tipo de documento: Article