What question did this study set out to answer?

To determine the binding affinity and selectivity of SJ874 for platelet glycoprotein IIb/IIIa (αIIbβ3) integrin and evaluate its antiplatelet efficacy relative to other antagonists and aspirin.

October 1, 2000Coronary Artery Disease

Human platelet αIIbβ3 integrin binding affinity and specificity of SJ874: antiplatelet efficacy versus aspirin

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Why the study?

Does SJ874 improve inhibition of platelet aggregation compared to aspirin in human platelets?

Population

Human cells and platelets from normal healthy volunteers

Comparison

SJ874 vs Aspirin and other glycoprotein IIb/IIIa…

Design

Preclinical

Authors

SMShaker A. MousaUniversity of North Carolina at Chapel Hill MFMark S. ForsytheDuPont (United States)JBJeffrey M. BozarthBristol-Myers Squibb (United States)

Discussion

Member takes

Implication

Warrants further in vivo testing; leaves open clinical translation of SJ874 versus aspirin.

Key Points

To determine the binding affinity and selectivity of SJ874 for platelet glycoprotein IIb/IIIa (αIIbβ3) integrin and evaluate its antiplatelet efficacy relative to other antagonists and aspirin.
Measured binding affinity and specificity for αIIbβ3 against other integrins (αvβ3, αvβ5, and α5β1) using human cell-adhesion and [125I]-fibrinogen binding assays.
Evaluated inhibition of platelet aggregation via light-transmittance and laser-scattering aggregometry, comparing SJ874 to other glycoprotein IIb/IIIa antagonists and to 325 mg oral aspirin administered to healthy volunteers.
SJ874 inhibited ADP-induced aggregation with a half-maximal concentration of 0.046 ± 0.005 µmol/l and [125I]-fibrinogen binding to activated platelets with a half-maximal concentration of 0.0012 ± 0.0005 µmol/l.
Laser-scattering aggregometry showed SJ874 totally inhibited both micro- and macro-aggregates stimulated by ADP or epinephrine, whereas 325 mg aspirin attenuated macro-aggregates but failed to prevent micro-aggregates.
SJ874 demonstrated high specificity for αIIbβ3 over other integrins (half-maximal concentration > 100 µmol/l) and bound resting human platelets more tightly than DMP754 and slightly less tightly than DMP802.

Structured PICO

Does SJ874 improve inhibition of platelet aggregation compared to aspirin in human platelets?

Population

Human cells and platelets from normal healthy volunteers

Intervention

SJ874 (nonpeptide glycoprotein IIb/IIIa antagonist)

Comparator

Aspirin (325 mg) and other glycoprotein IIb/IIIa antagonists (DMP754, DMP802)

Outcome

Binding affinity, specificity for platelet glycoprotein IIb/IIIa integrin, and antiplatelet efficacy (inhibition of aggregation)surrogate

SJ874 demonstrates potent, specific binding to human platelet glycoprotein IIb/IIIa and superior inhibition of platelet aggregation compared to aspirin in vitro.

Cite This Study

Mousa et al. (2000) studied this question.

synapsesocial.com/papers/6a8347dd8dce46bed9132433 https://doi.org/10.1097/00019501-200010000-00008

Topics

Dual antiplatelet therapy

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Human platelet αIIbβ3 integrin binding affinity and specificity of SJ874: antiplatelet efficacy versus aspirin

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Human platelet αIIbβ3 integrin binding affinity and specificity of SJ874: antiplatelet efficacy versus aspirin

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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