Veledimex (INXN-1001) (Synonyms: INXN-1001; RG-115932) |
رقم الكتالوجGC31791 |
فيليديمكس (INXN-1001)، وهو مشتق اصطناعي لهرمون تسلّق الحشرات إيكديزون، هو عامل تفعيل فموي نشط لنظام المروج الوراثية الخاص بالعلاج الجيني.
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Cas No.: 1093130-72-3
Sample solution is provided at 25 µL, 10mM.
Veledimex is an oral activator ligand for a proprietary gene therapy promoter system, and a moderate inhibitor of and substrate for CYP3A4/5.
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].
[1]. Cai H, et al. Plasma Pharmacokinetics of Veledimex, a Small-Molecule Activator Ligand for a Proprietary Gene Therapy Promoter System, in Healthy Subjects. Clin Pharmacol Drug Dev. 2017 May;6(3):246-257. [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.
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