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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Veledimex targets the ecdysone receptor (EcR), a nuclear receptor that is part of the RheoSwitch Therapeutic System (RTS). Upon administration, Veledimex specifically binds to the EcR located on the separately administered RTS. In the presence of Veledimex, the protein heterodimer changes to a stable conformation, forming an active transcription factor complex that can bind to the inducible promoter, thereby allowing the induction of controlled transcription of the target gene.
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| ln Vitro |
In vitro, Veledimex acts as an activator ligand for the ecdysone receptor-based inducible gene regulation system. It binds to the ecdysone receptor, forming a stable transcription factor complex that allows controlled transcription of the target gene. Its activity is assessed using cell-based reporter assays measuring the expression of target genes.
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| ln Vivo |
Following a single oral dosage in mice and monkeys, veledimex (INXN-1001) typically exhibits moderate to poor oral bioavailability (-56% in mice and up to 17.4% in cynomolgus monkeys), with primarily plasma elimination. reduced (between 1399 and 1170 mL/h). given intravenously, with a long terminal half-life (-10 hours in mice and 30 hours in monkeys), a high volume of distribution (20271 and 9180 mL/h in mice and monkeys, respectively), and both [1]. Ad-RTS-mIL-12 + Veledimex has shown dose-dependent expression of IL-12 mRNA and protein in tumors. In many syngeneic animal tumor models, IL-12 mRNA and protein expression returned to baseline upon stopping Veledimex. In both naïve and orthotopic GL-261 mice, veledimex passes the blood-brain barrier. Tumor-bearing mice exhibit brain tissue levels that are 6-7 times higher than those of normal mice. Ad-RTS-mIL-12 + veledimex showed a dose-related rise in survival that was free of serious side effects [2].
In vivo, Veledimex penetrates the blood-brain barrier (BBB) in situ in GL-261 mice and cynomolgus monkeys. It is used to activate certain genes using the ecdysone receptor (EcR)-based inducible gene regulation system, the RheoSwitch Therapeutic System (RTS). It has been studied for the treatment of melanoma and breast cancer. |
| Enzyme Assay |
In vitro receptor binding assays for Veledimex are performed using purified ecdysone receptor (EcR) protein. Binding affinity is measured using surface plasmon resonance (SPR) or fluorescence polarization. Functional assays measure the compound's ability to activate EcR-mediated transcription using reporter gene assays in cells expressing the receptor.
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| Cell Assay |
In vitro cellular assays for Veledimex are performed using cells expressing the ecdysone receptor and a reporter gene under the control of an EcR-inducible promoter. Cells are treated with the compound, and reporter gene expression (e.g., luciferase) is measured. The EC50 for activation of transcription is calculated from concentration-response curves.
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| Animal Protocol |
In vivo animal experiments for Veledimex are conducted in mouse models such as GL-261 glioma-bearing mice. A typical protocol involves administration of the compound (e.g., via oral or intraperitoneal routes) followed by assessment of target gene expression in tissues. BBB penetration is evaluated by measuring compound levels in brain tissue.
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| ADME/Pharmacokinetics |
Veledimex has a molecular weight of 438.60 and molecular formula C₂₇H₃₈N₂O₃. It is an orally active compound. It penetrates the blood-brain barrier. Further PK details, including half-life, bioavailability, and tissue distribution, are available from the manufacturer's data sheets.
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| Toxicity/Toxicokinetics |
Toxicological data for Veledimex are not extensively reported. As a research-use compound, its safety profile has not been formally evaluated in comprehensive preclinical toxicology studies. The compound is intended for research purposes only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
Veledimex has been used in clinical trials for the treatment of glioblastoma, metastatic breast cancer, and anaplastic oligoastrocytoma. Veledimex is a small, orally bioavailable dihydrazide activating ligand that can be used to activate specific genes in the RheoSwitch Therapeutic System (RTS), an inducible gene regulation system based on the ecdysone receptor (EcR). After administration, Veledimex specifically binds to the EcR located on the RTS when administered alone. The RTS comprises two fusion proteins: Gal4-EcR, which contains a modified ecdysone receptor (EcR) fused to the DNA-binding domain of the yeast Gal4 transcription factor; and VP16-RXR, which contains a chimeric retinoid X receptor (RXR) fused to the transcriptional activation domain of the herpes simplex virus type 1 (HSV1) viral protein VP16. In the absence of Veledimex, the fusion proteins form inactive, unstable, and nonfunctional heterodimers. In the presence of viridimer, the protein heterodimer transforms into a stable conformation, forming an active transcription factor complex that can bind to an inducible promoter, thereby inducing controlled transcription of the target gene.
Veledimex is also known as INXN-1001. It is an orally active activator ligand for the ecdysone receptor (EcR)-based inducible gene regulation system, the RheoSwitch Therapeutic System (RTS). It penetrates the BBB. This product is for research use only. |
| Molecular Formula |
C27H38N2O3
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| Molecular Weight |
438.6022
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| Exact Mass |
438.288
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| CAS # |
1093130-72-3
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| Related CAS # |
Veledimex (S enantiomer);1093131-03-3;Veledimex racemate;755013-59-3
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| PubChem CID |
57751161
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.451
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
32
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| Complexity |
605
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCC[C@H](C(C)(C)C)N(C(=O)C1=CC(=CC(=C1)C)C)NC(=O)C2=C(C(=CC=C2)OC)CC
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| InChi Key |
LZWZPGLVHLSWQX-XMMPIXPASA-N
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| InChi Code |
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
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| Chemical Name |
N'-(3,5-dimethylbenzoyl)-N'-[(3R)-2,2-dimethylhexan-3-yl]-2-ethyl-3-methoxybenzohydrazide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~57.00 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.70 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2800 mL | 11.3999 mL | 22.7998 mL | |
| 5 mM | 0.4560 mL | 2.2800 mL | 4.5600 mL | |
| 10 mM | 0.2280 mL | 1.1400 mL | 2.2800 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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