A Naphthalenic Derivative ND-1 Inhibits Thrombus Formation by Interfering the Binding of Fibrinogen to Integrin αIIbβ3.
Integrin αIIbβ3 plays a crucial role in the process of platelet aggregation. Three integrin αIIbβ3 antagonists (abciximab, eptifibatide, and tirofiban) have been approved by FDA for clinical use. Unfortunately, they all showed severe side effects such as thrombocytopenia and bleeding risk. Thus, res...
| Publicado en: | BioMed Research International Vol. 2016; pp. 1 - 9 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
12/20/2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=120314720&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 120314720 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 12/20/2016 vid: 2016 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 120314720 120314720 120314720 10.1155/2016/8587164 120314720 ppf: 1 ppct: 8 formats: fmt: @attributes: type: P tig: atl: A Naphthalenic Derivative ND-1 Inhibits Thrombus Formation by Interfering the Binding of Fibrinogen to Integrin αIIbβ3. aug: au: Ding, Xue Liu, Tong-dan Xie, Zhou-ling Zhao, Qi Cao, Yuan Liu, Xiao-dong Wang, Cai-hui Gamariel, Rwibasira Rudinga Ming, Xin Li, Zhi-yu Kong, Yi affil: School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Street, Nanjing 210009, China sug: subj: Fibrinogen Receptors, Cell Surface Thrombosis Drug Therapy Platelet Aggregation Inhibitors Administration and Dosage Hydrocarbons, Aromatic Administration and Dosage Drugs, Investigational Molecular Structure Hemorrhage Risk Factors Platelet Aggregation Drug Effects Collagen Administration and Dosage Thrombin Administration and Dosage Dose-Response Relationship, Drug Animal Studies Rats Human Biological Assay Enzyme-Linked Immunosorbent Assay Arteriovenous Shunt, Surgical Platelet-Rich Plasma Blood Platelets Descriptive Statistics Data Analysis Software Antigens, Surface One-Way Analysis of Variance Post Hoc Analysis P-Value Platelet Aggregation Inhibitors Adverse Effects Flow Cytometry Microscopy Methods Aspirin Administration and Dosage Funding Source ab: Integrin αIIbβ3 plays a crucial role in the process of platelet aggregation. Three integrin αIIbβ3 antagonists (abciximab, eptifibatide, and tirofiban) have been approved by FDA for clinical use. Unfortunately, they all showed severe side effects such as thrombocytopenia and bleeding risk. Thus, researches on the development of more effective and safer antiplatelet agents are needed. In this manuscript we reported a novel naphthalenic derivative compound ND-1 with potent antithrombotic effect and lower bleeding risk. ND-1 inhibited ADP-, collagen-, thrombin-, and U46619-induced platelet aggregation with IC50 values of 1.29, 14.46, 12.84, and 40.24 μM, respectively. Mechanism studies indicated that ND-1 inhibited the binding of fibrinogen to integrin αIIbβ3 in a dose-dependent manner with an IC50 value of 3.12 μM. ND-1 inhibited P-selectin expression induced by ADP, collagen, thrombin, and U46619 on the surface of platelets. Additionally, this compound reduced platelets spreading to the immobilized fibrinogen. In vivo, ND-1 potently decreased thrombus formation in an arteriovenous shunt thrombosis model in rats and slightly prolonged bleeding time in a tail cutting model in mice. Taken together, our results reveal that ND-1 is a novel antagonist of αIIbβ3 with strong antithrombotic effect and lower bleeding risk. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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