✽ Our Technology
Covalent selective inhibition of HPSE
We use bio-inspiration to design novel molecules that binds covalently and selectively to the active site of heparanase (HPSE). By using the enzyme's transition state to embed itself permanently in the active site pocket, it provides a novel mechanism designed to improve safety and reduce the off-target effects associated with non-selective competitive inhibitors.
The core of this technology lies in its approach as a mechanism-based covalent inhibitor, often called a "suicide substrate." VL166 is engineered to be recognized and processed by heparanase as if it were its natural substrate. However, as the enzyme initiates its catalytic action, it unmasks a reactive group on VL166, which then forms a permanent, irreversible bond with an amino acid in the active site.
This strategy ensures exquisite selectivity, as the inactivation is triggered only by HPSE's unique catalytic machinery. In essence, the enzyme is tricked into participating in its own permanent deactivation, providing a robust and highly targeted therapeutic effect.
Protein Data Bank: See more
We're applying VL166 in indications where HPSE overexpression is linked to disease. For more, visit our development programs.
