Smart thrombosis inhibitors without bleeding side effects via charge tunable ligand design, 2023, Chanel C La et al

Drug candidate stops blood clots w/o bleeding risk developed.

Abstract
Current treatments to prevent thrombosis, namely anticoagulants and platelets antagonists, remain complicated by the persistent risk of bleeding. Improved therapeutic strategies that diminish this risk would have a huge clinical impact. Antithrombotic agents that neutralize and inhibit polyphosphate (polyP) can be a powerful approach towards such a goal.

Here, we report a design concept towards polyP inhibition, termed macromolecular polyanion inhibitors (MPI), with high binding affinity and specificity. Lead antithrombotic candidates are identified through a library screening of molecules which possess low charge density at physiological pH but which increase their charge upon binding to polyP, providing a smart way to enhance their activity and selectivity.

The lead MPI candidates demonstrates antithrombotic activity in mouse models of thrombosis, does not give rise to bleeding, and is well tolerated in mice even at very high doses. The developed inhibitor is anticipated to open avenues in thrombosis prevention without bleeding risk, a challenge not addressed by current therapies.

https://www.nature.com/articles/s41467-023-37709-0

 

“The development of MPI 8 represents a major breakthrough in the field of blood clot prevention and treatment,” said co-lead investigator Jayachandran Kizhakkedathu, a professor and Canada Research Chair at UBC’s department of pathology and laboratory medicine and the UBC Centre for Blood Research, in a press statement.

https://www.insideprecisionmedicine...p-blood-clots-without-bleeding-risk-developed