| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
The compound targets vimentin, a key structural protein of the intermediate filament cytoskeleton, which is highly expressed in transformed mesenchymal cancer cells and plays a role in cell migration and mitosis. It exhibits selectivity for vimentin over other related proteins, making it a promising agent for targeting cancers of mesenchymal origin.
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| ln Vitro |
Vimentin-IN-1 (compound 4e) (0-10 mM; 72 h) is much more potent than FiVe1 (IC50=1.6 μM, HT-1080) at inhibiting HT-1080 fibrosarcoma, with an IC50 value of 44 nM [1]. Phosphorylation of VIM Ser56 is induced by venterin-IN-1 (0.1 μM; 24 hours) [1]. In mouse liver microsomes, ventin-IN-1 (100 μM) is less stable; after 60 minutes of incubation, 0.0% is still present [1]. Samples are taken at 0, 5, 15, 30, 45, and 60 minutes.
This compound potently inhibits the proliferation of HT-1080 fibrosarcoma cells with an IC50 of 44 nM, which is significantly more potent than the parent compound FiVe1 (IC50 = 1.6 microM). At a concentration of 0.1 microM for 24 hours, it effectively induces the hyperphosphorylation of vimentin at serine 56, a key pharmacodynamic marker of its on-target activity. |
| ln Vivo |
The oral pharmacokinetic properties of Vimentin-IN-1 (Compound 4e) (10 mg/kg; single dose) are superior to those of Five1 [1]. Vimentin-IN-1's pharmacokinetic characteristics in mice [1] The dosage by route (mg/kg) AUC0-last (ng·h/mL) AUC0-inf (ng·h/mL) T1/2 (hour) Tmax (h), Cmax (ng/mL), and Final (h) 4e PO 25 309.78 339.21 4.57 0. 5 18 110.43 PO 10 371.33 534.33 4.68 0.67 8 154.67 4e IP 1 208.33 211.33 0.59 0.25 4 197.00 Five1
Specific in vivo efficacy data for this exact compound is not detailed, but its parent compound (FiVe1) has shown efficacy in mouse xenograft models. The compound is described as orally bioactive and has better oral pharmacokinetic properties than FiVe1, suggesting potential for improved efficacy in animal models of fibrosarcoma and other mesenchymal cancers. |
| Enzyme Assay |
A typical biochemical assay for vimentin binding involves an ELISA-based approach. Recombinant vimentin protein is coated onto a plate. Serially diluted Anticancer agent 82 is incubated with biotinylated vimentin and streptavidin-conjugated horseradish peroxidase. After washing, the binding signal is developed and measured. The phosphorylation assay uses recombinant vimentin and an activated kinase in the presence of the compound, followed by detection of pSer56-vimentin via a phospho-specific antibody.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: HT-1080, RD and MCF-7 Cell Tested Concentrations: 0-10 mM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of HT-1080, RD and MCF-7 cells with IC50 of 44 nM, 61 nM and 49 nM respectively. To assess its mechanism, HT-1080 cells are seeded in 96-well plates and treated with varying concentrations of the compound for 72 hours. Cell viability is measured using a CCK-8 or MTT assay. To visualize the effect on the cytoskeleton and mitosis, cells are treated with 0.1 microM of the compound for 24 hours, fixed, and stained with a vimentin antibody and DAPI. Multinucleation and mitotic disruption are observed under a fluorescence microscope. |
| Animal Protocol |
For pharmacokinetic studies, a typical in vivo protocol involves a single oral administration of the compound (e.g., at 10 mg/kg) to fasted mice. Blood samples are collected via tail vein at various time points (e.g., 0, 0.5, 1, 2, 4, 8, and 24 hours post-dose). Plasma concentrations of the compound are quantified using a validated LC-MS/MS method to determine PK parameters.
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| ADME/Pharmacokinetics |
After a single oral dose of 10 mg/kg in mice, Anticancer agent 82 demonstrates superior PK properties compared to FiVe1, with an AUC0-last of 371.33 ng·h/mL, a terminal half-life (T1/2) of 4.68 hours, a time to reach maximum concentration (Tmax) of 0.67 hours, and a maximum plasma concentration (Cmax) of 154.67 ng/mL. This profile indicates improved oral bioavailability.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Anticancer agent 82 are not detailed in the available literature. However, its selective mechanism targeting vimentin-overexpressing mesenchymal cancer cells suggests it may have a better safety profile than traditional chemotherapeutics that target dividing cells indiscriminately. Standard in vivo studies would monitor body weight and organ histopathology.
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| References | |
| Additional Infomation |
The compound represents a novel strategy for selectively targeting mesenchymal cancers by disrupting the vimentin intermediate filament network during mitosis. As a research chemical with improved oral pharmacokinetics over its predecessor, it is a valuable tool for cancer biology studies. As of the latest updates, it has not yet progressed to clinical trials or been approved for medical use.
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| Molecular Formula |
C19H18CL2N4O
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|---|---|
| Molecular Weight |
389.278421878815
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| Exact Mass |
388.085
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| CAS # |
2319587-80-7
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| PubChem CID |
156552418
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| Appearance |
Light yellow to orange solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
463
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC(=CC(=C1)N2CCN(CC2)C3=CN=NC4=C3C=CC=C4Cl)Cl
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| InChi Key |
JWIRSMDIIXNJAU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H18Cl2N4O/c1-26-15-10-13(20)9-14(11-15)24-5-7-25(8-6-24)18-12-22-23-19-16(18)3-2-4-17(19)21/h2-4,9-12H,5-8H2,1H3
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| Chemical Name |
8-chloro-4-[4-(3-chloro-5-methoxyphenyl)piperazin-1-yl]cinnoline
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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 (~64.22 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.42 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5688 mL | 12.8442 mL | 25.6885 mL | |
| 5 mM | 0.5138 mL | 2.5688 mL | 5.1377 mL | |
| 10 mM | 0.2569 mL | 1.2844 mL | 2.5688 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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