Last update 01 Nov 2024

αvβ3 x GP IIb/IIIa

Last update 01 Nov 2024

Basic Info

Related Targets

αvβ3GP IIb/IIIa

Drugs associated with αvβ3 x GP IIb/IIIa

SKF-107260

Target

GP IIb/IIIa x αvβ3

Mechanism

GP IIb/IIIa antagonists [+1]

Active Org.-

Originator Org.

Smithkline Beecham Plc

Active Indication-

Inactive Indication

Thromboembolism

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SC-56631

Target

GP IIb/IIIa x αvβ3

Mechanism

GP IIb/IIIa antagonists [+1]

Active Org.-

Originator Org.

Pharmacia Corp.

Active Indication-

Inactive Indication

Thrombosis

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MN-447

Target

GP IIb/IIIa x αvβ3

Mechanism

GP IIb/IIIa antagonists [+1]

Active Org.-

Originator Org.

Meiji Seika Pharma Co., Ltd.

Active Indication-

Inactive Indication

Myocardial Infarction [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with αvβ3 x GP IIb/IIIa

100 Translational Medicine associated with αvβ3 x GP IIb/IIIa

0 Patents (Medical) associated with αvβ3 x GP IIb/IIIa

113

Literatures (Medical) associated with αvβ3 x GP IIb/IIIa

14 Jan 2016·Current Drug MetabolismQ4 · MEDICINE

Effects Of Glycoprotein IIb/IIIa Antagonists: Anti Platelet Aggregation And Beyond

Q4 · MEDICINE

Review

Author: Enrico Coscioni ; Maria Fiammetta Romano ; Roberta Rossini ; Giuseppe Musumeci ; Anna D'Angelillo ; Giuseppe Biondi Zoccai ; Arturo Giordano ; Stefano Messina ; Simona Romano

BACKGROUNDThe use of inhibitors of glycoprotein IIb/IIIa (GPIIb/IIIa) has provided dramatic results in terms of the prevention of acute stent thrombosis and a reduction in major adverse coronary events in patients subjected to percutaneous coronary intervention. GPIIb/IIIa or αIIbβ3 is a member of the β3 subfamily of integrins, which also includes αVβ3. GPIIb/IIIa functions as a receptor for fibrinogen and several adhesion proteins sharing an arginine-glycine-aspartic acid (RGD) sequence. GPIIb/IIIa antagonists, through blockade of the receptor, prevent platelet aggregation. Among the three GPIIb/IIIa antagonists used in therapy, abciximab is an anti-β3 monoclonal antibody, while tirofiban and eptifibatide mimic the binding sequence of the fibrinogen ligand. Although antiplatelet aggregation represents the central function of GPIIb/IIIa inhibitors, further actions have been documented for these compounds.OBJECTIVEThe aim of the present article is to review the structures and functions of GPIIb/IIIa antagonists and to highlight the clinical outcomes and results of randomized trials with these compounds. Hypotheses on the unexplored potential of GPIIb/IIIa antagonists will be put forward.CONCLUSIONGPIIb/IIIa inhibitors were developed to prevent platelet aggregation, however, these compounds can exert further biological functions, both platelet- and non-platelet-related. Large-scale studies comparing the efficacy and safety of GPIIb/IIIa antagonists are lacking. More insights into the functions of these compounds may lead to generation of novel small molecules able to antagonize platelet aggregation while promoting vascular repair.

01 Mar 2014·Cancer LettersQ1 · MEDICINE

Roles for GP IIb/IIIa and αvβ3 integrins in MDA-MB-231 cell invasion and shear flow-induced cancer cell mechanotransduction

Q1 · MEDICINE

Article

Author: Wu, Chunhui ; Liu, Yiyao ; Guan, Liuyuan ; Zhao, Fenglong ; Yang, Hong ; Li, Li

Adhesion of cancer cell to endothelial cells and the subsequent trans-endothelial migration are key steps in hematogenous metastasis. However, the molecular mechanisms of cancer cell/endothelial cell interaction under hemodynamic shear flow and how shear flow-induced cancer cell mechanotransduction are yet to be fully defined. In this study, we identified that the integrins of both platelet glycoprotein IIb/IIIa (GP IIb/IIIa) and αvβ3 were crucial for hematogenous metastasis of human breast carcinoma MDA-MB-231 cells. The cell migration and invasion were studied by using Millicell cell culture insert system. The numbers of invaded MDA-MB-231 cells significantly increased by thrombin-activated platelets and reduced by eptifibatide, a platelet inhibitor. Meanwhile, RGDWE peptides, a specific inhibitor of αvβ3 integrin, also inhibited MDA-MB-231 cell invasion. We further used a parallel-plate flow chamber to investigate MDA-MB-231 cell adhesion under flow conditions. Alike in static condition, the adhesion capability of MDA-MB-231 cells to endothelial monolayer was also significantly affected by GP IIb/IIIa and αvβ3 integrins. The expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and αvβ3 integrin in MDA-MB-231 cells were up-regulated after low shear stress exposure (1.84 dynes/cm(2), 2 h). Moreover, we also demonstrated that low shear stress induced a sustained activation of p85 (a regulatory subunit of PI3K) and Akt. Pre-treating MDA-MB-231 cells with the specific PI3K inhibitor of LY294002 abolished the shear stress induced-Akt activation, and the expression of MMP-2, MMP-9, vascular endothelial growth factor (VEGF) and αvβ3 integrin were also down-regulated. Immunofluorescence assay showed that low shear stress also induced αvβ3 integrin clustering and nuclear factor-κB (NF-κB) activation. Interestingly, shear stress-induced activation of Akt and NF-κB was attenuated by LM609, a specific antibody of αvβ3 integrin. It suggests that αvβ3 integrin might be as a mechanosensor to trigger both PI3K/Akt and NF-κB signaling pathways. Taken together, these results establish that GP IIb/IIIa and αvβ3 integrins are essential mediators, and provide insight into how shear stress-induced αvβ3 integrin activation and the downstream pathways for contribution to MDA-MB-231 cell adhesion, migration and invasion.

01 Jul 2010·HaematologicaQ1 · MEDICINE

L718P mutation in the membrane-proximal cytoplasmic tail of 3 promotes abnormal IIb 3 clustering and lipid microdomain coalescence, and associates with a thrombasthenia-like phenotype

Q1 · MEDICINE

Article

Author: Lastres, Pedro ; Martinez, Constantino ; Rivera, Jose ; Conde, Isabel ; Gonzalez-Manchon, Consuelo ; Vicente, Vicente ; Jayo, Asier

BACKGROUNDSupport for the role of transmembrane and membrane-proximal domains of alpha IIb beta 3 integrin in the maintenance of receptor low affinity comes from mutational studies showing that activating mutations can induce constitutive bi-directional transmembrane signaling.DESIGN AND METHODSWe report the functional characterization of a mutant alpha IIb beta 3 integrin carrying the Leu718Pro mutation in the membrane-proximal region of the beta 3 cytoplasmic domain, identified in heterozygosis in a patient with a severe bleeding phenotype and defective platelet aggregation and adhesion.RESULTSTransiently transfected cells expressed similar levels of normal and mutant alpha IIb beta 3, but surface expression of mutant alpha v beta 3 was reduced due to its retention in intracellular compartments. Cells stably expressing mutant alpha IIb beta 3 showed constitutive binding to soluble multivalent ligands as well as spontaneous fibrinogen-dependent aggregation, but their response to DTT was markedly reduced. Fibrinogen-adherent cells exhibited a peculiar spreading phenotype with long protrusions. Immunofluorescence analysis revealed the formation of alpha IIb beta 3 clusters underneath the entire cell body and the presence of atypical high-density patches of clustered alpha IIb beta 3 containing encircled areas devoid of integrin that showed decreased affinity for the fluorescent lipid analog DiIC(16) and were disrupted in cholesterol-depleted cells.CONCLUSIONSThese findings are consistent with an important role of the membrane-proximal region of beta 3 in modulating alpha IIb beta 3 clustering and lateral redistribution of membrane lipids. Since the beta 3 mutant was associated with a thrombasthenic phenotype in a patient carrying one normal beta 3 allele, these results support a dominant role of clustering in regulating integrin alpha IIb beta 3 functions in vivo.

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