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  • Title: Abciximab (ReoPro, chimeric 7E3 Fab) demonstrates equivalent affinity and functional blockade of glycoprotein IIb/IIIa and alpha(v)beta3 integrins.
    Author: Tam SH, Sassoli PM, Jordan RE, Nakada MT.
    Journal: Circulation; 1998 Sep 15; 98(11):1085-91. PubMed ID: 9736595.
    Abstract:
    BACKGROUND: Large, randomized, and blinded clinical trials (EPIC, EPILOG, and CAPTURE) have demonstrated that abciximab (ReoPro, chimeric 7E3 Fab) markedly reduces thrombotic events associated with percutaneous transluminal coronary interventions. The marked early benefits at 30 days were sustained at 6 months and 3 years. Initially developed because of its efficacy in blocking GP IIb/IIIa (alphaIIb/beta3) receptors on platelets, abciximab also binds with equivalent affinity to alpha(v)beta3. METHODS AND RESULTS: This study presents a detailed characterization of the alphavss3 interaction, including the ability of abciximab to (1) bind with comparable affinity to alpha(v)beta3 and GP IIb/IIIa, (2) inhibit alpha(v)beta3 and GP IIb/IIIa-mediated cell adhesion in vitro with IC50 values approximating binding KD values, and (3) redistribute between GP IIb/IIIa and alpha(v)beta3 integrins in vitro. CONCLUSIONS: As an antagonist of not only GP IIb/IIIa but also alpha(v)beta3, abciximab may provide additional clinical benefit in preventing alpha(v)beta3-mediated effects such as thrombin generation, clot retraction, or smooth muscle cell migration and proliferation. Abciximab binds with equivalent affinity to both GP IIb/IIIa and alphavss3 and redistributes between the 2 integrin receptors in vitro. Abciximab has been previously shown to circulate on platelets for up to 2 weeks. Taken together, these findings suggest that abciximab may have the ability to inhibit both GP IIb/IIIa and alpha(v)beta3 for extended periods.
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