Evidence map›Paper›PMID 41070786›Full record

ArticleChemMedChem2025

Potent Antisickling Furaldehyde Analogs for Acute Sickle Cell Therapy: Enhanced Efficacy and Intravenous Formulation Potential.

Abdelsattar M Omar, Moustafa E El-Araby, Tarek A Ahmed, Akua K Donkor, Albert Opare, Mohini S Ghatge, Anfal S Aljahdali, Rana T Alhashimi, Trevohn N Robinson, Benita Balogun and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Abdelsattar M OmarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Moustafa E El-ArabyDepartment of Medicinal Chemistry, School of Pharmacy and the Center for Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.ORCID https://orcid.org/0000-0002-7932-2226
Tarek A AhmedDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Akua K DonkorDepartment of Medicinal Chemistry, School of Pharmacy and the Center for Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.
Albert OpareDepartment of Medicinal Chemistry, School of Pharmacy and the Center for Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.
Mohini S GhatgeDepartment of Medicinal Chemistry, School of Pharmacy and the Center for Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.
Anfal S AljahdaliDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Rana T AlhashimiDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Trevohn N RobinsonDepartment of Medicinal Chemistry, School of Pharmacy and the Center for Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.
Benita BalogunDivision of Hematology, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA, 19104, USA.
Mariana MaciasDivision of Hematology, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA, 19104, USA.
Salma RolandDivision of Hematology, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA, 19104, USA.
Yan ZhangDepartment of Medicinal Chemistry, School of Pharmacy and the Center for Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.
Faik N MusayevDepartment of Medicinal Chemistry, School of Pharmacy and the Center for Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.
Osheiza AbdulmalikDivision of Hematology, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA, 19104, USA.ORCID https://orcid.org/0000-0003-2497-4291
Martin K SafoDepartment of Medicinal Chemistry, School of Pharmacy and the Center for Drug Discovery, Virginia Commonwealth University, Richmond, VA, 23219, USA.ORCID https://orcid.org/0000-0002-9536-1743

Funding

Targeted Identification of Dual Acting Antisickling Agents for Sickle Cell Disease TherapyR61HL156158 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI ABDULMALIK, OSHEIZA Y, SAFO, MARTIN K · 2021 to 2022
$1.1M
X-ray Crystallographic Data Collection SystemS10OD021756 · OD · VIRGINIA COMMONWEALTH UNIVERSITY · PI SAFO, MARTIN K · 2017 to 2017
$600k
Institutional Fund Projects IFPNC-002-166-2020Ministry of Education and King Abdulaziz University, Jeddah, Saudi ArabiaNational Institutes of Health (NHLBI) R61HL156158NHLBI NIH HHS R61 HL156158NIH HHS S10 OD021756NIH Shared Instrumentation S10OD021756Virginia Commonwealth University (MKS)Virginia General Assembly Higher Education Equipment Trust Fund (HEETF)
6 · The paper itself

Abstract

Sickle cell disease (SCD) is a debilitating inherited blood disorder characterized by acute crises that require immediate intervention. Aromatic aldehydes that increase hemoglobin (Hb) oxygen affinity (e.g., 5-HMF) can prevent hypoxia-induced erythrocyte sickling, but clinical efforts have been hindered by insufficient potency or poor pharmacokinetics. Herein, analogs of 5-HMF (MMA-500 series of compounds) are reported to retain 5-HMF positive physicochemical and pharmacodynamic properties, including safety, solubility, and relatively short duration of action that are essential for their acute use. Two analogs, MMA503 and MMA509, demonstrate over 3.3-fold greater in vitro antisickling activity than 5-HMF. This potency is evidenced by significantly enhanced Hb adduct formation, increased oxygen affinity, and robust inhibition of red blood cell sickling in sickle blood assays. X-ray crystallography further elucidates the Hb binding interactions underlying their potency at the molecular level. MMA509 emerges as a lead candidate and is advanced to formulation studies. An IV formulation of MMA509 in 40% polyethylene glycol 400 achieves ≈13.5 mg mL

Indexed as

AldehydesAnemia, Sickle CellAntisickling AgentsAdministration, IntravenousAnimalsCrystallography, X-RayDose-Response Relationship, DrugHumansMolecular StructureStructure-Activity RelationshipAldehydesAntisickling Agents5‐HMF analogsacute crisesantisicklingaromatic aldehydeshemoglobinsickle cell diseaseX‐ray crystallography

Identifiers

PMID41070786
PMCPMC12640667

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.