Compounds for the Inhibition of Kifc3, Methods of Making the Same, and Pharmaceutical Compositions Comprising the Same

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This patent discloses a new class of compounds that selectively inhibit KIFC3, a specific motor protein involved in platelet production, and their pharmaceutical compositions. The invention focuses on treating diseases associated with abnormal KIFC3 function, such as neonatal thrombocytopenia, delayed platelet recovery following umbilical cord blood stem cell transplantation, and Down syndrome-associated myeloid neoplasms. The compounds can be administered to patients (including neonates) to increase endogenous platelet production, and are also applicable for ex vivo generation of platelets for transfusion.

Use CasesContent extracted from patent full text and abstract with AI.

• Treatment of neonatal thrombocytopenia to reduce or eliminate the need for platelet transfusions in premature or critically ill newborns.
• Accelerating platelet recovery following umbilical cord blood stem cell transplantation to improve patient outcomes and reduce mortality and morbidity.
• Targeted therapy for Down syndrome-associated myeloid neoplasm (TAM and ML-DS), potentially reducing the need for cytotoxic chemotherapy.
• Ex vivo generation of platelets from stem cell sources for use as transfusion products, addressing shortages and immunological issues in platelet supply.
• Enhancement of platelet production in individuals with other forms of thrombocytopenia or impaired platelet function.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides a targeted, non-toxic pharmacologic approach to stimulate endogenous platelet production without the risks associated with current therapies (e.g., thrombopoietin receptor agonists).
• Reduces reliance on adult platelet transfusions, lowering risks such as immune reactions, infection, and volume overload in newborns.
• Improves outcomes and speeds platelet recovery post cord blood transplantation, an area where current treatments have limited effectiveness.
• Enables large-scale, reliable ex vivo production of platelets for transfusion, helping to alleviate shortages and provide customized HLA-matched or HLA-null transfusion products.
• Demonstrates specificity for megakaryocyte lineage and minimal effects on other blood cell development, providing a safer side effect profile.

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Inventors & Applicants

Patent Abstract

In one aspect, the disclosure relates to compounds and pharmaceutical compositions for treating diseases or disorders associated with aberrant Kifc3 function in a subject. In a further aspect, the disease or disorder can be selected from neonatal thrombocytopenia, delayed platelet recovery following umbilical cord blood stem cell transplantation, Down syndrome-associated myeloid neoplasm, or any combination thereof. In one aspect, the subject can be a human, including a neonatal human, and performing the method increases platelet production in the subject. Also disclosed are methods for ex vivo platelet production using the disclosed compounds and pharmaceutical compositions.