A novel anti-platelet peptide (Z4A5) potential for glycoprotein IIb/IIIa inhibits platelet aggregation

Li, Yingxue; Sun, Qiang; Zhang, Hui; Ren, Shuting; Liao, Yue‐Yuan; Wang, Ya; Shen, Xin-Liang; Wang, Bing

doi:10.1016/j.thromres.2012.02.047

Cited by 13 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Platelet aggregation was measured as previously described using a four-channel aggregometer (LBY-NJ4, Pulisheng Science Instrument Company, Beijing, China) [9, 16]. Briefly, PRP was centrifuged at 1580 ×g for 10 min to obtain platelet-poor plasma (PPP).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A Naphthalenic Derivative ND-1 Inhibits Thrombus Formation by Interfering the Binding of Fibrinogen to Integrin αIIbβ3

Ding

Liu

Xie

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Both inside-out and outside-in signaling in platelet involve this molecule [7, 8]. So the activation of integrin α IIb β 3 was recognized as the final common pathway of platelet aggregation [9, 10]. Three integrin α IIb β 3 antagonists (abciximab, eptifibatide, and tirofiban) have been approved by FDA for clinical use.…”

Section: Introductionmentioning

confidence: 99%

A Naphthalenic Derivative ND-1 Inhibits Thrombus Formation by Interfering the Binding of Fibrinogen to Integrin αIIbβ3

Ding

Liu

Xie

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…This sequence is purported to antagonize the platelet GP IIb/IIIa receptor with high affinity. The potential benefits of this drug include its ability to bind reversibly which is advantageous for treating patients at high risk for bleeding . A novel peptide Pro‐Ser‐Nva‐Gly‐Asp‐Trp (Z4A5) was found to inhibit platelet aggregation and the formation of platelet thrombi.…”

Section: Preclinical Evidence Of Antiplatelet Peptidesmentioning

confidence: 99%

“…The potential benefits of this drug include its ability to bind reversibly which is advantageous for treating patients at high risk for bleeding. 97,98,100 A novel peptide Pro-Ser-Nva-Gly-Asp-Trp (Z4A5) was found to inhibit platelet aggregation and the formation of platelet thrombi. The activity of Z4A5 on fibrinogen and PAC-1 (an IgM monoclonal antibody) binding to GP IIb/IIIa was studied.…”

Section: Synthetic Peptidesmentioning

confidence: 99%

Bioactive peptides and proteins as alternative antiplatelet drugs

Rengasamy

Khan

Ahmad

et al. 2019

Medicinal Research Reviews

View full text Add to dashboard Cite

Antiplatelet drugs reduce the risks associated with atherothrombotic events and show various applications in diverse cardiovascular diseases including myocardial infarctions. Efficacy of the current antiplatelet medicines including aspirin, clopidogrel, prasugrel and ticagrelor, and the glycoprotein IIb/IIIa antagonists, are limited due to their increased risks of bleeding, and antiplatelet drug resistance. Hence, it is important to develop new effective antiplatelet drugs, with fewer side‐effects. The vast repertoire of natural peptides can be explored towards this goal. Proteins and peptides derived from snake venoms and plants represent exciting candidates for the development of novel and potent antiplatelet agents. Consequently, this review discusses multiple peptides that have displayed antiplatelet aggregation activity in preclinical drug development stages. This review also describes the antiplatelet mechanisms of the peptides, emphasizing the signaling pathways intervened by them. Also, the hurdles encountered during the development of peptides into antiplatelet drugs have been listed. Finally, hitherto unexplored peptides with the potential to prevent platelet aggregation are explored.

show abstract

“…Z4A5, a new platelet GP IIb/IIIa receptor antagonist, is a linear peptide with double RGD recognition sequences (Li et al ., ). This compound was synthesized as an analogue of a previously identified series of GP IIb/IIIa antagonists designed as a mimetic of the α‐chain of fibrinogen.…”

Section: Introductionmentioning

confidence: 97%

Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina

Jing¹,

Li²,

Zhang³

et al. 2013

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEThe glycoprotein IIb/IIIa receptor is the final common pathway of platelet aggregation, regardless of the agonist, and thus represents an ideal therapeutic target for blocking coronary thrombosis. In this study, the anti-platelet and antithrombotic actions of Z4A5, a new glycoprotein IIb/IIIa receptor inhibitor, were evaluated in a canine model of acute unstable angina. EXPERIMENTAL APPROACHZ4A5 was given i.v. as a bolus followed by 60 min of continuous infusion at doses of 30 mg·kg -1 + 1 mg·kg. Its antithrombotic effect was evaluated in a model of coronary thrombosis, the injured, stenosed left circumflex coronary artery, in which platelet-dependent cyclic flow reductions (CFRs) were induced by vascular compression and constriction to simulate clinical acute unstable angina. Platelet aggregation and coagulation parameters were determined in platelet-rich plasma and platelet poor plasma respectively. KEY RESULTSThe Z4A5 infusion induced a dose-dependent reduction in CFR frequency, which returned to baseline levels after the termination of the infusion at low doses. At medium dose that inhibited most part of platelet aggregation, it increased tongue bleeding time marginally with no dramatic changes in haemodynamic and coagulation parameters. Furthermore, the inhibition of ADP-induced platelet aggregation and prolonged bleeding time observed during Z4A5 infusion reverted to baseline levels after the termination of the infusion. CONCLUSIONS AND IMPLICATIONSZ4A5 is an effective antithrombotic agent for coronary artery thrombosis with a rapid-on and rapid-off pharmacological profile, and could be used as an alternative treatment of coronary artery ischaemic syndromes.

show abstract

A novel anti-platelet peptide (Z4A5) potential for glycoprotein IIb/IIIa inhibits platelet aggregation

Cited by 13 publications

References 31 publications

A Naphthalenic Derivative ND-1 Inhibits Thrombus Formation by Interfering the Binding of Fibrinogen to Integrin αIIbβ3

A Naphthalenic Derivative ND-1 Inhibits Thrombus Formation by Interfering the Binding of Fibrinogen to Integrin αIIbβ3

Bioactive peptides and proteins as alternative antiplatelet drugs

Antithrombotic effect of Z4A5 on coronary thrombosis in a canine model of acute unstable angina

Contact Info

Product

Resources

About