VT00065 is a covalent DHS inhibitor. VT00065 forms a redox-dependent covalent bond with the catalytic lysine K329 of DHS, locking the enzyme in an inactive state [1].
In Vitro, VT00065 (100 mM; 24 h) covalently and specifically modifies the catalytic K329 residue of purified human DHS, suggesting it acts as a mechanism-based binder with potential to irreversibly inactivate the enzyme, though it exhibits low binding occupancy[1]. VT00065 (2-20 mM; 9 min) exhibits weak, dose-dependent inhibition of deoxyhypusination activity in purified human DHS-eIF5A reactions[1].
References:
[1]. Wilk P, et al. Crystallographic fragment screening supports tool compound discovery and reveals conformational flexibility in human deoxyhypusine synthase. Commun Chem. 2026;9(1):66. Published 2026 Jan 17.
In Vitro, VT00065 (100 mM; 24 h) covalently and specifically modifies the catalytic K329 residue of purified human DHS, suggesting it acts as a mechanism-based binder with potential to irreversibly inactivate the enzyme, though it exhibits low binding occupancy[1]. VT00065 (2-20 mM; 9 min) exhibits weak, dose-dependent inhibition of deoxyhypusination activity in purified human DHS-eIF5A reactions[1].
References:
[1]. Wilk P, et al. Crystallographic fragment screening supports tool compound discovery and reveals conformational flexibility in human deoxyhypusine synthase. Commun Chem. 2026;9(1):66. Published 2026 Jan 17.