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January 12, 2022Advanced ScienceOpen Access

Targeting the RT loop of Src SH3 in Platelets Prevents Thrombosis without Compromising Hemostasis

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Why the study?

Conventional antiplatelet agents increase bleeding risk by indiscriminately inhibiting thrombosis and hemostasis, and identifying a specific druggable target to block integrin αIIbβ3 outside-in signaling in vivo remains an unproven challenge.

Does DCDBS84 prevent thrombosis without compromising hemostasis in mice?

Population

In vitro and in vivo mouse models

Comparison

DCDBS84 vs high doses of αIIbβ3 antagonist

Design

Preclinical in vitro and in vivo mutational and pharmacological study

Authors

KZKongkai ZhuZLZhangbiao LongHZHuimin Zhang

Discussion

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Member takes

Overview

May separate antithrombotic efficacy from bleeding risk in mice; leaves open translation of Src SH3 targeting to human therapy.

Structured PICO

Does DCDBS84 prevent thrombosis without compromising hemostasis in mice?

P
Population
In vitro models and mice
I
Intervention
DCDBS84 (small molecule targeting the RT loop of Src SH3)
C
Comparator
Control / high doses of αIIbβ3 antagonist
O
Outcome
Inhibition of thrombosis and primary hemostasissurrogate

DCDBS84 demonstrates that targeting the RT loop of Src SH3 can prevent thrombosis without increasing bleeding risk in preclinical models.

Cite This Study

Zhu et al. (2022) studied this question.

synapsesocial.com/papers/6a881141afcf99b77fbbf6e1https://doi.org/10.1002/advs.202103228
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Structure-guided design of pure orthosteric inhibitors of αIIbβ3 that prevent thrombosis but preserve hemostasis2020 · 56 citations
  2. 2Combined Accelerated Tissue-Plasminogen Activator and Platelet Glycoprotein IIb/IIIa Integrin Receptor Blockade With Integrilin in Acute Myocardial Infarction1997 · 380 citations
  3. 3WASP plays a novel role in regulating platelet responses dependent on αIIbβ3 integrin outside‐in signalling2009 · 37 citations
  4. 4Targeting Integrin and Integrin Signaling in Treating Thrombosis2014 · 132 citations
  5. 5Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy2005 · 260 citations