Completed Heart, Stroke & Blood Cancer

Lead identification of a novel anticoagulant agent targeted against activated factor XII for the prevention of thrombosis without the risk of bleeding associated with current antithrombotics

In plain English

AI plain-English summary

Blood thinners that prevent dangerous clots also make patients bleed—a team at the University of Leeds is hunting for a compound that blocks clotting without that risk. Current anticoagulants, used by millions to prevent strokes and heart attacks, force a trade-off: enough drug to stop a clot can also cause uncontrolled bleeding, sometimes fatal. Patients require regular monitoring to keep that balance. The researchers aim to sidestep the problem entirely by targeting Factor XIIa, a protein that kick-starts clot formation but, based on strong evidence, is not needed for normal wound healing. Blocking it should prevent thrombosis without impairing the body’s ability to stop bleeding. With a £3,021,002 Wellcome Seeding Drug Discovery award, the team will screen for small molecules that inhibit Factor XIIa, then refine them into a daily oral pill. If successful, the drug could replace current therapies for conditions like atrial fibrillation or deep-vein thrombosis, eliminating the need for blood tests and reducing hospital visits. The work is applied drug discovery, not fundamental science—the goal is a specific medicine, not a general insight.

View original technical description
At the University of Leeds, Dr Helen Philippou (PI) and Prof Robert Ariens (Faculty of Medicine and Health), with colleagues (Faculty of Mathematics and Physical Sciences) Dr Richard Foster and Prof Colin Fishwick with Prof Gregory Lip (University of Birmingham) have secured a £3,021,002 Wellcome Trust Seeding Drug Discovery award to develop new safer anticoagulants with minimal risk of bleeding. The medicines available to treat patients who suffer from an increased risk of blood clotting are effective but carry a significant risk of causing bleeding. Current treatments therefore involve a balance between reducing blood clots with inducing bleeding. The objective of this proposal is to discover highly specific compounds which block a protein, Factor XIIa, which is involved in clot formation, and for which there is good evidence to suggest inhibition will not cause bleeding. This will allow patients to be treated more safely with minimal risk of bleeding without needing therapeutic monitoring. The aim is to produce an agent which will be given by mouth daily.

View the original record at the funder ↗

Researchers

Helen Philippou (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Development of First-In Class Small Molecule Preclinical Candidate Anticoagulant Targeting Activated Factor XII with Minimal Risk of Bleeding
Development and characterisation of mode of action of first-in class anticoagulant small molecules with no bleeding risk: Identification of lead candidate
Continuity Award of Development of First-in class small molecule preclinical candidate anticoagulant targeting activated factor XII with minimal risk of bleeding -105439
Identification of small molecule GPVI inhibitors as anti-platelet agents for the treatment of thrombosis with minimal bleeding risk
Optimisation of coagulation factor XIIa inhibitors as potential anticoagulants devoid of bleeding side effects

Original classification

Seeding Drug Discovery Award

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