What is the clinical evidence from this study?

Study design: Other. Intervention: DMP728. Primary outcome: inhibition of human platelet aggregation (IC50 = 0.046 microM).

What question did this study set out to answer?

To determine the binding affinity, antiplatelet efficacy, and receptor selectivity of DMP728, a novel cyclic peptide antagonist of platelet GPIIb/IIIa.

November 18, 2008Cardiology

Antiplatelet Efficacy and Specificity of DMP728, a Novel Platelet GPIIb/llla Receptor Antagonist

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Key result

DMP728 is a novel antiplatelet agent that demonstrated high affinity and specificity for platelet GPIIb/IIIa, inhibiting human platelet aggregation with an IC50 of 0.046 µM.

Population

Human platelets and purified human GPIIb/IIIa (in vitro)

Design

Preclinical

Authors

SMShaker A. MousaUniversity of North Carolina at Chapel Hill JBJeff M. BozarthDuPont (United States)MFMark S. ForsytheDuPont (United States)

Discussion

Member takes

Implication

Supports preclinical development of DMP728; leaves open clinical translation as a GPIIb/IIIa antagonist.

Key Points

To determine the binding affinity, antiplatelet efficacy, and receptor selectivity of DMP728, a novel cyclic peptide antagonist of platelet GPIIb/IIIa.
Assessed inhibition of human platelet aggregation stimulated by various agonists using light transmittance aggregometry and electrical impedance techniques.
Measured competitive binding to purified GPIIb/IIIa via ELISA, 3H-DMP728 binding affinity in intact human platelets, and displacement of 125I-fibrinogen binding.
Evaluated selectivity against non-target surface receptors, including endothelial vitronectin receptors (alpha v/beta 3), platelet GPIb/IX, and leukocyte integrins.
DMP728 inhibited human platelet aggregation across diverse agonists with an IC50 of 0.046 ± 0.002 µM and exhibited active deaggregatory capabilities.
The compound blocked 125I-fibrinogen binding to platelets with an IC50 of 2.3 ± 0.8 nM, displaying high-affinity binding in ELISA (Ki = 0.4 nM) and intact platelets (Kd = 0.1 nM).
Binding proved highly specific for platelet GPIIb/IIIa over endothelial vitronectin receptors, platelet GPIb/IX, and leukocyte integrin complexes.

Structured PICO

Population

Human platelets and purified human GPIIb/IIIa (in vitro)

Intervention

DMP728 (a cyclic methane sulfonate GPIIb/IIIa receptor antagonist)

Outcome

Inhibition of human platelet aggregation, 125I-fibrinogen binding, binding affinity, and specificity for GPIIb/IIIasurrogate

Main Result

Effect estimate: IC50 = 0.046 microM

DMP728 is a novel, highly specific, and potent in vitro antagonist of the platelet GPIIb/IIIa receptor.

Cite This Study

Mousa et al. (2008) studied this question. DMP728 was evaluated on inhibition of human platelet aggregation (IC50 = 0.046 microM). DMP728 is a novel antiplatelet agent that demonstrated high affinity and specificity for platelet GPIIb/IIIa, inhibiting human platelet aggregation with an IC50 of 0.046 µM.

synapsesocial.com/papers/6a93f656cd4df3c00e007bca https://doi.org/10.1159/000175994

Topics

Dual antiplatelet therapy

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Antiplatelet Efficacy and Specificity of DMP728, a Novel Platelet GPIIb/llla Receptor Antagonist

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Topics

Antiplatelet Efficacy and Specificity of DMP728, a Novel Platelet GPIIb/llla Receptor Antagonist

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

Topics

Also Consider