Discovery of Heparin Mimetic, Potent, and Selective Inhibitors of Human Clotting Factor XIIIa.

ABSTRACT: Factor XIIIa (FXIIIa) is a cysteine transglutaminase that catalyzes the last step in the coagulation process. An anion-binding site inhibition of FXIIIa is a paradigm-shifting strategy that may offer key advantages of controlled inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We previously reported a flavonoid trimer-based allosteric inhibitor of FXIIIa with moderate potency and selectivity. To further advance this approach, we evaluated a series of 27 variably sulfonated heparin mimetics against human FXIIIa. Only 13 molecules exhibited inhibitory activity at the highest concentration tested with IC₅₀ values of 2-286 μM. Specifically, inhibitor 16 demonstrated an IC₅₀ value of 2.4 ± 0.5 μM in a bisubs

SUBMITTER: Vu KT 

PROVIDER: S-EPMC11256326 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature