A Novel KGD-Based αIIbβ3 Antagonist Prevents Arterial Thrombosis While Preserving Hemostasis and Avoiding Thrombocytopenia.

ABSTRACT: Current αIIbβ3 antagonists are potent antithrombotic agents, their clinical use is limited by the risk of life-threatening bleeding. Emerging evidence has highlighted key mechanistic differences between thrombosis and hemostasis, opening avenues for safer antithrombotic strategies. Targeting integrin αIIbβ3 outside-in signaling has been proposed to mitigate bleeding risk; however, the short half-life of peptide-based therapeutics remains a major challenge. In this study, we developed an optimized αIIbβ3 antagonist, KGDRR-a recombinant mutant protein derived from snake venom disintegrin, incorporating an Arg55 residue within the KGD loop-through systematic structure-activity relationship (SAR) analysis. Molecular docking revealed a critical cation-π interaction between Arg55 of KGDRR and Ty

SUBMITTER: Kuo YJ 

PROVIDER: S-EPMC12111684 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature