ArticlePurinergic signalling2009
Progress in the discovery of selective, high affinity A(2B) adenosine receptor antagonists as clinical candidates.
Article in Purinergic signalling, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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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.
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Who cites it
25 citing papers in PubMed, 53 citations in OpenAlex.
- A2BAR Antagonism Mitigates Pulmonary Inflammation and Fibrosis and Restores Macrophage M1/M2 Balance in Diabetic Rats.International journal of molecular sciences · 2026Article
- Ligand and Residue Free Energy Perturbations Solve the Dual Binding Mode Proposal for an AThe journal of physical chemistry. B · 2025Article
- A2B Adenosine Receptor in Idiopathic Pulmonary Fibrosis: Pursuing Proper Pit Stop to Interfere with Disease Progression.International journal of molecular sciences · 2023Review
- Kinetic profiling and functional characterization of 8-phenylxanthine derivatives as ABiochemical pharmacology · 2022Article
- International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update.Pharmacological reviews · 2022Review
- Exploiting the Indole Scaffold to Design Compounds Binding to Different Pharmacological Targets.Molecules (Basel, Switzerland) · 2020Review
- G Protein-Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action.Pharmacological reviews · 2020Review
- Small molecules as theranostic agents in cancer immunology.Theranostics · 2019Review
- Characterisation of endogenous ABiochemical pharmacology · 2018Article
- Targeting A2 adenosine receptors in cancer.Immunology and cell biology · 2017Review
- Trial Watch-Small molecules targeting the immunological tumor microenvironment for cancer therapy.Oncoimmunology · 2016Review
- Big opportunities for small molecules in immuno-oncology.Nature reviews. Drug discovery · 2015Review
- Article
- Discovery of 3,4-Dihydropyrimidin-2(1H)-ones As a Novel Class of Potent and Selective A2B Adenosine Receptor Antagonists.ACS medicinal chemistry letters · 2013Article
- Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Adenosine signaling during acute and chronic disease states.Journal of molecular medicine (Berlin, Germany) · 2013Review
- The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Recent developments in adenosine receptor ligands and their potential as novel drugs.Biochimica et biophysica acta · 2011Review
- Xanthines as adenosine receptor antagonists.Handbook of experimental pharmacology · 2011Review
- Role of adenosine A(2B) receptors in inflammation.Advances in pharmacology (San Diego, Calif.) · 2011Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The selective, high affinity A(2B) adenosine receptor (AdoR) antagonists that were synthesized by several research groups should aid in determining the role of the A(2B) AdoR in inflammatory diseases like asthma or rheumatoid arthritis (RA) and angiogenic diseases like diabetic retinopathy or cancer. CV Therapeutics scientists discovered the selective, high affinity A(2B) AdoR antagonist 10, a 8-(4-pyrazolyl)-xanthine derivative [CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM] that has favorable pharmacokinetic (PK) properties (t (1/2) = 4 h and F > 35% rat). Compound 10 demonstrated functional antagonism at the A(2B) AdoR (K(B) = 6 nM) and efficacy in a mouse model of asthma. In two phase 1 clinical trials, CVT-6883 was found to be safe, well tolerated, and suitable for once daily dosing. A second compound 20, 8-(5-pyrazolyl)-xanthine, has been nominated for development from Baraldi's group in conjunction with King Pharmaceuticals that has favorable A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 1,000; and K(i)(hA(3)) > 1,000 nM], and it has been demonstrated to be a functional antagonist. A third compound 32, a 2-aminopyrimidine, from the Almirall group has high A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM], and 32 has been moved into preclinical safety testing. Since three highly selective, high affinity A(2B) AdoR antagonists have been nominated for development with 10 (CVT-6883) being the furthest along in the development process, the role of the A(2B) AdoR in various disease states will soon be established.
Identifiers
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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.