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IQCA-TAVV: To explore the effect of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8 on deep venous thrombosis. | LitMetric

IQCA-TAVV: To explore the effect of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8 on deep venous thrombosis.

Oncotarget

Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, PR China.

Published: October 2017

AI Article Synopsis

  • Deep vein thrombosis (DVT) can lead to serious health issues, and current treatments are limited, prompting research into a new compound, IQCA-TAVV, designed to inhibit DVT.
  • IQCA-TAVV shows promise by targeting P-selectin and GPIIb/IIIa and effectively inhibiting activated platelet aggregation in a concentration-dependent manner.
  • The compound also demonstrates anti-inflammatory effects comparable to aspirin and does not cause harm to major organs at tested doses, suggesting its potential as a safe treatment option for DVT.

Article Abstract

Deep vein thrombosis (DVT) associates with considerable morbidity, functional disability and mortality. Due to the lack of suitable inhibitor the correlation of various factors in DVT onset remains unknown. In this context we analyzed the structure of anti-platelet aggregation agent, P-selectin down-regulator, GPIIb/IIIa down-regulator and anti-inflammatory agent, thereby designed N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)- Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA-TAVV) as an inhibitor of DVT to receive evaluations. The docking predicted that IQCA-TAVV can target P-selectin and GPIIb/IIIa. The UV showed that IQCA-TAVV can act on P-selectin and GPIIb/IIIa. ELISA indicated that IQCA-TAVV concentration dependently inhibited activated platelets to express P-selectin and GPIIb/IIIa, and the minimal effective concentration was 1 nM. IC of IQCA-TAVV against platelet aggregation induced by arachidonic acid, adenosine diphosphate and platelet activating factor fell within a range of 0.13 nM to 0.30 nM. IQCA-TAVV dose-dependently inhibited venous thrombosis and the minimal effective dose was 1 nmol/kg. On ear edema model the anti-inflammation activity of 10 nmol/kg IQCA-TAVV equaled that of 1.1mmol/kg aspirin. The concentration of IL-2, IL-6 and IL-8 in the serum of the ear edema mice were also significantly decreased by 10 nmol/kg IQCA-TAVV. Even at 1 μmol/kg of dose IQCA-TAVV still did not injure the kidney, the liver, and the nerves of healthy mice. Thereby IQCA-TAVV depicts a relationship of three levels (inhibiting platelet activation, targeting externalized membrane receptor, decreasing serum inflammatory factor) for the down-regulation of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8 in DVT.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710932PMC
http://dx.doi.org/10.18632/oncotarget.20588DOI Listing

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