Veledimex (S enantiomer)

1093131-03-3

C27H38N2O3

10 mM in DMSO

Immunology/Inflammation; Metabolic Enzyme/Protease

Veledimex S enantiomer is the S enantiomer of veledimex. Veledimex is an oral activator ligand for a proprietary gene therapy promoter system, and a moderate inhibitor of and substrate for CYP3A4/5. In Vivo: Veledimex generally has moderate to low oral bioavailability after a single oral administration in mice and monkeys (-56% in mice and up to 17.4% in cynomolgus monkeys) with mostly low plasma clearance (1399 and 1170 mL/h per kilogram in mice and monkeys, respectively), high volume of distribution (20271 and 9180 mL/h per kilogram in mice and monkeys, respectively), and long terminal half-lives (-10 hours in mice and -30 hours in monkeys) after intravenous administration^[1]. Ad-RTS-mIL-12 + veledimex have demonstrated a dose-related increase in tumor IL-12 mRNA and IL-12 protein expression. Discontinuation of veledimex resulted in a return to baseline IL-12 mRNA and protein expression in numerous syngeneic mouse tumor models. Veledimex crosses the blood-brain-barrier in both naive and orthotopic GL-261 mice with increased brain tissue level of -6 fold observed in tumor bearing vs. normal mice. Ad-RTS-mIL-12 + veledimex demonstrate a dose-related increase in survival without significant adverse events^[2].