Virginia Commonwealth University

The Children's Hospital of Philadelphia

King Abdulaziz University

Illexcor Holdings, LLC

Osheiza Abdulmalik

Martin K Safo

Yan Zhang

Moustafa Elsayed El-Araby

Mohini Ghatge

Guoyan Xu

Abdelsattar Mansour Omar

Moustafa El-Sayed El-Araby

Jurgen Venitz

Abdelsattar Mansour Ebid Omar

Abdelsatter M Omar

Piyusha Pradeep Pagare

Andrew Fleischman

David Light

Compounds and methods for preventing and/or treating one or more symptoms of sickle cell diseases (SCD) by administering at least one of the compounds are provided. The compounds are chemically modified to increase bioavailability and activity, e.g., so that the compounds prevent adhesion and sickling of red blood cells (RBCs).

Benzaldehyde compounds with direct polymer destabilizing effects to treat sickle cell disease

Methods for administering compounds provide a rapid treatment for sickle cell disease (SCD) to inhibit or reverse red blood cell sickling. The compounds are a group of 5-hydroxymethylfurfural (5-HMF) analogs modified to increase water-solubility. The compounds can be formulated in an aqueous carrier and administered intravenously for immediate uptake into red blood cells (RBCs) within hours, rather than days or weeks. In vitro experiments demonstrated rapid uptake into RBCs and increased Oaffinity of HbS to an equilibrium point within 30 to 90 minutes. The compounds have a desired level of safety as well as a short half-life, both of which are compatible with acute usage. Thus, the methods of treatment rapidly achieve therapeutic steady-state drug levels, making it possible to deliver a treatment in critical emergency care situations to prevent, reverse and otherwise treat acute sickling or anemia.

Methods for using 5-HMF analogs with increased solubility to inhibit or reverse RBC sickling

Compounds and methods for preventing and/or treating one or more symptoms of sickle cell diseases (SCD) by administering at least one of the compounds are provided. The compounds are based on vanillin which is chemically modified to increase bioavailability and activity, e.g. so that the compounds bind to the F helix of hemoglobin (Hb) and prevent adhesion of red blood cells (RBCs).

Aromatic aldehydes with sustained and enhanced in vitro and in vivo pharmacologic activity to treat sickle cell disease

Prodrugs and derivatives of 5-hydoxymethyl-2-furfural (5-HMF) with protected or modified aldehyde and/or alcohol moieties are provided. The prodrugs or derivatives exhibit increased bioavailability, e.g. due to having extended half-lives in circulation. The drugs are therefore administered i) at lower doses and/or ii) less frequently than 5-HMF, while still maintaining the beneficial therapeutic effects of 5-HMF.

Prodrug and protected forms of 5-hydroxymethylfurfuranal (5-HMF) and its derivatives

Azolylacryloyl derivatives with hypoxic properties are provided. The compounds have a generic formula: and are suitable for treating sickle cell disease and hypoxia-underlying diseases, e.g. hemorrhagic and traumatic shock, cardiac arrest and cardiogenic shock, traumatic brain injury, cancer, stroke, myocardial infarction, myocardial ischemia, vaso-occlusive crisis, etc. 

Azolylacryloyl derivatives as therapeutic agents for sickle cell disease

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Philadelphia, PA, United States of America

Osheiza Abdulmalik