ArticleBlood2008
Application of high-throughput screening to identify a novel alphaIIb-specific small- molecule inhibitor of alphaIIbbeta3-mediated platelet interaction with fibrinogen.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 68 citations in OpenAlex.
- Conformational response of αStructure (London, England : 1993) · 2025Article
- Integrins as Drug Targets in Vascular and Related Diseases.International journal of drug discovery and pharmacology · 2024Article
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- INTEGRINS: A BEDSIDE TO BENCH TO BEDSIDE STORY.Transactions of the American Clinical and Climatological Association · 2023Article
- Application of Auxiliary VerifyNow Point-of-Care Assays to Assess the Pharmacodynamics of RUC-4, a Novel αIIbβ3 Receptor Antagonist.TH open : companion journal to thrombosis and haemostasis · 2021Article
- Electron microscopy shows that binding of monoclonal antibody PT25-2 primes integrin αIIbβ3 for ligand binding.Blood advances · 2021Article
- Berberine and Its Main Metabolite Berberrubine Inhibit Platelet Activation Through Suppressing the Class I PI3Kβ/Rasa3/Rap1 Pathway.Frontiers in pharmacology · 2021Article
- Standardization and Validation of Fluorescence-Based Quantitative Assay to Study Human Platelet Adhesion to Extracellular-Matrix in a 384-Well Plate.International journal of molecular sciences · 2020Article
- Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations.ACS pharmacology & translational science · 2019Article
- Preclinical Studies of RUC-4, a Novel Platelet αIIbβ3 Antagonist, in Non-Human Primates and With Human Platelets.Journal of clinical and translational science · 2019Article
- Morphometric analysis of spread platelets identifies integrin αScientific reports · 2018Article
- αIIbβ3 binding to a fibrinogen fragment lacking the γ-chain dodecapeptide is activation dependent and EDTA inducible.Blood advances · 2017Article
- The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling.Acta pharmacologica Sinica · 2016Article
- A Naphthalenic Derivative ND-1 Inhibits Thrombus Formation by Interfering the Binding of Fibrinogen to IntegrinBioMed research international · 2016Article
- Anti-thrombotic agents derived from snake venom proteins.Thrombosis journal · 2016Review
- αIIbβ3: structure and function.Journal of thrombosis and haemostasis : JTH · 2015Review
- Targeting integrin and integrin signaling in treating thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2015Review
- RUC-4: a novel αIIbβ3 antagonist for prehospital therapy of myocardial infarction.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- Article
- A novel class of ion displacement ligands as antagonists of the αIIbβ3 receptor that limit conformational reorganization of the receptor.Bioorganic & medicinal chemistry letters · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Small-molecule alphaIIbbeta3 antagonists competitively block ligand binding by spanning between the D224 in alphaIIb and the MIDAS metal ion in beta3. They variably induce conformational changes in the receptor, which may have undesirable consequences. To identify alphaIIbbeta3 antagonists with novel structures, we tested 33 264 small molecules for their ability to inhibit the adhesion of washed platelets to immobilized fibrinogen at 16 muM. A total of 102 compounds demonstrated 50% or more inhibition, and one of these (compound 1, 265 g/mol) inhibited ADP-induced platelet aggregation (IC(50): 13+/- 5 muM), the binding of soluble fibrinogen to platelets induced by mAb AP5, and the binding of soluble fibrinogen and a cyclic RGD peptide to purified alphaIIbbeta3. Compound 1 did not affect the function of GPIb, alpha2beta1, or the other beta3 family receptor alphaVbeta3. Molecular docking simulations suggest that compound 1 interacts with alphaIIb but not beta3. Compound 1 induced partial exposure of an alphaIIb ligand-induced binding site (LIBS), but did not induce exposure of 2 beta3 LIBS. Transient exposure of purified alphaIIbbeta3 to eptifibatide, but not compound 1, enhanced fibrinogen binding ("priming"). Compound 1 provides a prototype for small molecule selective inhibition of alphaIIbbeta3, without receptor priming, via targeting alphaIIb.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.