The Disintegrin Echistatin Stabilizes Integrin αIIbβ3's Open Conformation and Promotes Its Oligomerization

Toxinas provenientes de venenos de serpiente: blancos terapéuticos, herramientas en investigación biomédica y agentes con potencial terapéutico

“…Investigadores tomaron la estructura de las desintegrinas como molde para el diseño de moléculas que se unen con alta afinidad al receptor mencionado, dando como resultado la aprobación de dos nuevos medicamentos, el Eptifibatide (Integrilin ® ) y el Tirofiban (Agrastat ® ). El primero se modeló a partir del sitio activo de la barbourina (Sistrurus barbouri), que de hecho es una proteína que contiene el motivo kdg [55], mientras que el segundo se diseñó a partir de la echistatina (desintegrina que posee el motivo rdg) [56,57]. Ambos fármacos han sido aprobados en la terapia de la isquemia coronaria aguda y en la prevención de trombosis en pacientes a los que se les realizó una intervención coronaria tal como angioplastia o inserción de un stent [58,59].…”

Contrast Ultrasound and Targeted Microbubbles: Diagnostic and Therapeutic Applications for Angiogenesis

“…Targeting of α V -integrins have been accomplished using either monoclonal antibodies (mAb) targeted against α V -integrins or arginine-glycinearspartate (RGD) containing peptides that have a strong affinity for select integrins, such as α V β 3 . Both of these targeting strategies have been demonstrated in autoradiographic, PET, and MRI imaging of tumor vasculature [13,14]; however, immunogenicity concerns limit translation of mAb strategies to the clinical setting and suboptimal targeting specificity limits application of peptide-based strategies [15]. Microbubbles targeting α V -integrins were first observed by intravital microscopy of a mouse cremaster muscle after inducing angiogenesis with fibroblast growth factor (FGF)-2-eluting pellets [12].…”

Snake venom components and their applications in biomedicine

“…This resulted in the introduction of two drugs, eptifibatide and tirofiban. Eptifibatide (integrelin) was modelled on the active site of barbuorin, (Sistrurus m. barbouri) and is, in fact, a KGD-containing protein [58], while tirofiban (Aggrastat) which was designed from echistatin (a disintegrin) is a synthetic compound that mimics RGD [59,60]. Both drugs have been approved for the therapy of acute coronary ischaemic syndrome and the prevention of thrombotic complications in patients undergoing percutaneous coronary intervention such as balloon angioplasty and stenting [61,62].…”