Veledimex (S enantiomer)

• CAT Number: I013444
• CAS Number: 1093131-03-3
• Molecular Formula: C27H38N2O3
• Molecular Weight: 438.60
• Purity: ≥95%
• Synonyms: N’-(3,5-dimethylbenzoyl)-N’-[(3S)-2,2-dimethylhexan-3-yl]-2-ethyl-3-methoxybenzohydrazide
• InChI: InChI=1S/C27H38N2O3/c1-9-12-24(27(5,6)7)29(26(31)20-16-18(3)15-19(4)17-20)28-25(30)22-13-11-14-23(32-8)21(22)10-2/h11,13-17,24H,9-10,12H2,1-8H3,(H,28,30)/t24-/m0/s1
• InChIKey: LZWZPGLVHLSWQX-DEOSSOPVSA-N
• SMILES: CCCC(C(C)(C)C)N(C(=O)C1=CC(=CC(=C1)C)C)NC(=O)C2=C(C(=CC=C2)OC)CC

Veledimex S enantiomer (INXN-1001 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[1].
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].

Reference

[1]. Barrett JA, et al. Regulated intratumoral expression of IL-12 using a RheoSwitch Therapeutic System® (RTS®) gene switch as gene therapy for the treatment of glioma. Cancer Gene Ther. 2018;25(5-6):106-116.
 [Content Brief]

[2]. John A. Barrett, INTRATUMORAL REGULATED EXPRESSION OF IL-12 AS A GENE THERAPY APPROACH TO TREATMENT OF GLIOMA. Neuro Oncol. 2015 Nov; 17(Suppl 5): v113.