Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C27H38N2O3 |
Molecular Weight | 438.6022 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCC[C@@H](N(NC(=O)C1=CC=CC(OC)=C1CC)C(=O)C2=CC(C)=CC(C)=C2)C(C)(C)C
InChI
InChIKey=LZWZPGLVHLSWQX-XMMPIXPASA-N
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-/m1/s1
Veledimex is an oral activator ligand for a proprietary gene therapy promoter system, and a moderate inhibitor of and substrate for CYP3A4/5. Veledimex controls the expression of the target gene. The amount of gene product produced by the system and the duration of the effect is dependent on veledimex dose level and duration of dosing. Nonclinical studies demonstrated that intratumoral administration of Ad-RTS-IL12 along with oral administration of veledimex elicited dose-dependent anti-tumor effects in murine melanoma, breast cancer and glioma models which correlated with increased plasma exposure of veledimex. The FDA granted Fast Track designation for Ad-RTS-hIL-12 plus veledimex for the treatment of recurrent or progressive glioblastoma multiforme in adults. Ad-RTS-hIL-12 is an inducible adenoviral vector encoding human pro-inflammatory cytokine interleukin-12 (IL-12), which is under the transcriptional control of the RheoSwitch Therapeutic System. Veledixmex is an oral activator ligand. Data previously presented suggest that Ad-RTS-hIL-12 with 20 mg veledimex improves the median overall survival from 6 to 9 months seen with available therapies to 12.7 months, with further improvement in median overall survival to 17.8 months in a subset of subjects with reduced cumulative steroid exposure during the active dosing period of veledimex. Veledimex has been used in trials studying the treatment of glioblastoma multiforme, metastatic breast cancer, and anaplastic oligoastrocytoma.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29755109
Curator's Comment: Veledimex crossed the blood-brain barrier in both orthotopic GL-261 mice and cynomolgus monkeys.
Approval Year
PubMed
Title | Date | PubMed |
---|---|---|
Plasma Pharmacokinetics of Veledimex, a Small-Molecule Activator Ligand for a Proprietary Gene Therapy Promoter System, in Healthy Subjects. | 2017 May |
|
Regulated intratumoral expression of IL-12 using a RheoSwitch Therapeutic System(®) (RTS(®)) gene switch as gene therapy for the treatment of glioma. | 2018 Jun |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27364771
RTS-M103 study: an open label multiple-dose study in normal male subjects was performed to
assess the safety and tolerability of a 200 mg dose of veledimex as well as the safety and
tolerability of dosing vehicle, F-22, used for formulation. 200 mg veledimex was formulated
in soft gelatin capsules as an oral solution in F-22 formulation at a concentration of 30
mg/mL. Veledimex (200 mg) was administered orally. For best efficacy, veledimex should be administered in the
fed state to ensure optimal absorption and sufficient systemic exposure.
Route of Administration:
Oral
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FDA ORPHAN DRUG |
493815
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NCI_THESAURUS |
C2141
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ACTIVE MOIETY