# Inhibitors of Human Factor XIIIa as New Anticoagulants

> **NIH GM R16** · XAVIER UNIVERSITY OF LOUISIANA · 2026 · $150,000

## Abstract

SUMMARY
The long-term goal of our research is to develop effective anticoagulants that do not cause bleeding
complications to be safely used for a wider range of patients suffering from venous thromboembolism (VTE).
This project aims at developing effective and safer anticoagulants by targeting human factor XIIIa (FXIIIa). All
available anticoagulants are associated with a significant risk of bleeding. Current anticoagulants inhibit directly
or indirectly thrombin and/or factor Xa. This is the reason why they are clinically effective, but it is also the
reason why they cause bleeding. The central hypothesis is that inhibiting FXIIIa will result in effective
protection against VTE without causing significant bleeding. In contrast to all other clotting factors which are
serine proteases, FXIIIa is a transglutaminase that catalyzes the last step in the coagulation process. This
unique biochemical aspect of FXIIIa has been under investigation in the context of VTE. In vitro experiments
showed that treating normal human blood with an experimental transglutaminase inhibitor increases RBC
extrusion from contracting clots and reduces clot size. Various studies also suggested that a certain FXIIIa
polymorphism provides significant protection against VTE and that heterozygous FXIII-deficient mice do not
show signs of excessive bleeding. Thus, FXIIIa may serve as a potential therapeutic target to develop a new
effective treatment for VTE that does not significantly increase the bleeding risk. Despite this promise, very few
FXIIIa inhibitors have been developed, all of which lack substantial selectivity as they can also inhibit other
transglutaminases by blocking their active sites. Thus, I have proposed sulfonated non-saccharide glycos-
aminoglycan mimetics as a platform to develop FXIIIa inhibitors. The sulfonated molecules are to inhibit FXIIIa
potently and selectively through allosteric modulation. In preliminary studies, I discovered two sulfonated
molecules that inhibit F

## Key facts

- **NIH application ID:** 11322563
- **Project number:** 5R16GM149412-04
- **Recipient organization:** XAVIER UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Rami A Al-Horani
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $150,000
- **Award type:** 5
- **Project period:** 2023-04-17T00:00:00 → 2027-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11322563

## Citation

> US National Institutes of Health, RePORTER application 11322563, Inhibitors of Human Factor XIIIa as New Anticoagulants (5R16GM149412-04). Retrieved via AI Analytics 2026-05-20 from https://api.ai-analytics.org/grant/nih/11322563. Licensed CC0.

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