ReviewBritish journal of haematology2016
New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo?
Review in British journal of haematology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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.
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.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease.British journal of clinical pharmacology · 2019Trial
- Trial
- HypoxyStat, a small-molecule form of hypoxia therapy that increases oxygen-hemoglobin affinity.Cell · 2025Article
- Hemoglobin Variants as Targets for Stabilizing Drugs.Molecules (Basel, Switzerland) · 2025Review
- The antisickling agent, 5-hydroxymethyl-2-furfural: Other potential pharmacological applications.Medicinal research reviews · 2024Review
- Gene-environmental influence of space and microgravity on red blood cells with sickle cell disease.NPJ genomic medicine · 2024Review
- Biophysical chemistry behind sickle cell anemia and the mechanism of voxelotor action.Scientific reports · 2024Article
- Targeted modification of furan-2-carboxaldehydes into Michael acceptor analogs yielded long-acting hemoglobin modulators with dual antisickling activities.Chemical biology & drug design · 2024Article
- Quantitative assessment of the in-vitro binding kinetics of antisickling aromatic aldehydes with hemoglobin A: A universal HPLC-UV/Vis method to quantitate Schiff-base adduct formation.Journal of pharmaceutical and biomedical analysis · 2023Article
- X-ray crystallography and sickle cell disease drug discovery-a tribute to Donald Abraham.Frontiers in molecular biosciences · 2023Review
- Design, Synthesis, and Antisickling Investigation of a Nitric Oxide-Releasing Prodrug of 5HMF for the Treatment of Sickle Cell Disease.Biomolecules · 2022Article
- Isolation and Characterisation of Quercitrin as a Potent Anti-Sickle Cell Anaemia Agent fromJournal of clinical medicine · 2022Article
- Modulating hemoglobin allostery for treatment of sickle cell disease: current progress and intellectual property.Expert opinion on therapeutic patents · 2022Review
- Dietary-Nutraceutical Properties of Oat Protein and Peptides.Frontiers in nutrition · 2022Review
- Caffeic acid: an antioxidant with novel antisickling properties.FEBS open bio · 2021Article
- Article
- Improving the Solubility and Oral Bioavailability of a Novel Aromatic Aldehyde Antisickling Agent (PP10) for the Treatment of Sickle Cell Disease.Pharmaceutics · 2021Article
- MWC allosteric model explains unusual hemoglobin-oxygen binding curves from sickle cell drug binding.Biophysical journal · 2021Article
- MetAP2 inhibition modifies hemoglobin S to delay polymerization and improves blood flow in sickle cell disease.Blood advances · 2021Article
- Anti-hypoxia effects of walnut oligopeptides (American journal of translational research · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The hallmark of sickle cell disease is the polymerization of sickle haemoglobin due to a point mutation in the β-globin gene (HBB). Under low oxygen saturation, sickle haemoglobin assumes the tense (T-state) deoxygenated conformation that can form polymers, leading to rigid erythrocytes with impaired blood vessel transit, compounded or initiated by adhesion of erythrocytes to endothelium, neutrophils and platelets. This process results in vessel occlusion and ischaemia, with consequent acute pain, chronic organ damage, morbidity and mortality. Pharmacological agents that stabilize the higher oxygen affinity relaxed state (R-state) and/or destabilize the lower oxygen affinity T-state of haemoglobin have the potential to delay the sickling of circulating red cells by slowing polymerization kinetics. Relevant classes of agents include aromatic aldehydes, thiol derivatives, isothiocyanates and acyl salicylates derivatives. The aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF) increases oxygen affinity of sickle haemoglobin and reduces hypoxia-induced sickling in vitro and protects sickle cell mice from effects of hypoxia. It has completed pre-clinical testing and has entered clinical trials as treatment for sickle cell disease. A related molecule, GBT440, has shown R-state stabilization and increased oxygen affinity in preclinical testing. Allosteric modifiers of haemoglobin as direct anti-sickling agents target the fundamental pathophysiological mechanism of sickle cell disease.
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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.