| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
EOAI3402143 Tosylate selectively inhibits the deubiquitinases Usp9x, Usp24, and Usp5. By inhibiting these DUBs, the compound disrupts the ubiquitin-proteasome system, leading to the accumulation of ubiquitinated proteins and the induction of apoptosis in tumor cells. It acts as a dose-dependent inhibitor, fully blocking or regressing myeloma tumors in mice.
|
|---|---|
| ln Vitro |
Strong Usp9x and Usp5 inhibitory action is retained by EOAI3402143 [1]. Tumor cell apoptosis is increased and Usp9x and Usp24 activities are dose-dependently inhibited by EOAI3402143 [2]. When UM-2, UM-6, UM-16, and UM-76 were treated with the Usp9x inhibitor EOAI3402143 (G9), cell survival was dose-dependently reduced in comparison to the untreated vehicle; however, UM-2 3D colony growth control was entirely blocked by 600 nM EOAI3402143.
In vitro, EOAI3402143 Tosylate is a potent inhibitor of Usp9x, Usp24, and Usp5 activity. It acts in a dose-dependent manner, increasing tumor cell apoptosis. Its activity can be assessed using biochemical assays with purified DUB enzymes and ubiquitinated substrates, as well as in cell-based assays measuring apoptosis and cell viability. |
| ln Vivo |
The impact of EOAI3402143 (G9) therapy on human MIAPACA2 tumor xenografts was investigated in order to investigate this possibility. NSG mice received subcutaneous injections of human MIAPCA2 cells. Caliper measurements were used to track the primary tumor development. Once the tumor was detectable, mice were split into two groups and given either 15 mg/kg of G9 or a vehicle control (PEG300/DMSO). While receiving treatment, keep an eye on the animal's body weight, temperament, and tumor growth. Simultaneously, mice bearing 8041 tumors were generated and subjected to G9 therapy and tumor observation protocols akin to those employed with human MIAPACA2 xenografts. Usp9x inhibition inhibited the growth of tumors in human tumor xenografts, which is consistent with in vitro studies. However, there was no discernible effect on the growth of tumors in 8041 tumor xenografts; however, EOAI3402143 treatment effectively inhibited the growth of tumors in both human MIAPACA2 and 2 Usp9x activity. and 8041 xenograft tumors in mice [3].
In vivo, EOAI3402143 Tosylate has been shown to fully block or regress myeloma tumors in mice. It increases tumor cell apoptosis. Its antitumor activity has been demonstrated in preclinical models, highlighting its potential as a therapeutic agent for cancer. |
| Enzyme Assay |
Non-cellular enzyme assays for EOAI3402143 Tosylate involve assessing its inhibition of deubiquitinase (DUB) activity using purified recombinant Usp9x, Usp24, and Usp5 enzymes. The enzyme is incubated with a ubiquitinated substrate (e.g., Ub-AMC) in the presence of varying concentrations of EOAI3402143 Tosylate. The release of the fluorophore (AMC) is measured, and the IC₅₀ for inhibition of DUB activity is determined from dose-response curves.
|
| Cell Assay |
In vitro cellular assays for EOAI3402143 Tosylate involve treating cancer cell lines, such as myeloma cells, with the compound and measuring apoptosis and cell viability. Cells are exposed to varying concentrations of EOAI3402143 Tosylate for a defined period. Apoptosis is assessed by flow cytometry using Annexin V/PI staining or by measuring caspase activity. Cell viability is measured using MTT or CellTiter-Glo® assays.
|
| Animal Protocol |
In vivo animal experiments with EOAI3402143 Tosylate are conducted in mouse xenograft models of myeloma. Tumor-bearing mice are treated with EOAI3402143 Tosylate via oral or intraperitoneal administration. Tumor growth inhibition is monitored by caliper measurements. At study termination, tumors are collected for histopathological analysis and assessment of apoptosis markers.
|
| ADME/Pharmacokinetics |
EOAI3402143 Tosylate has a molecular weight of 675.62 and a molecular formula of C₃₂H₃₆Cl₂N₄O₆S. It is a light yellow to yellow solid powder. The compound is soluble in DMSO. For storage, the powder should be kept at -20°C for up to 3 years. It is stable under recommended storage conditions.
|
| Toxicity/Toxicokinetics |
EOAI3402143 Tosylate is a research compound for laboratory use only and is not approved for human therapeutic use. In preclinical studies, it has been generally well-tolerated at therapeutic doses. As a DUB inhibitor, it may have effects on the ubiquitin-proteasome system in normal cells. Standard laboratory safety precautions should be followed when handling the compound.
|
| References |
|
| Additional Infomation |
EOAI3402143 Tosylate (CAS 1699750-95-2) is a potent, dose-dependent inhibitor of the deubiquitinases Usp9x, Usp24, and Usp5. It increases tumor cell apoptosis and fully blocks or regresses myeloma tumors in mice. EOAI3402143 Tosylate is a valuable tool for studying DUB function and cancer biology, available from various commercial suppliers.
|
| Molecular Formula |
C32H36CL2N4O6S
|
|---|---|
| Molecular Weight |
675.622445106506
|
| Exact Mass |
674.173
|
| CAS # |
1699750-95-2
|
| Related CAS # |
1699750-95-2;
|
| PubChem CID |
91669215
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
4.5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
34
|
| Complexity |
714
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1=CC=C(N=C1/C=C(\C#N)/C(NC(C1C=CC(=CC=1)OCCN1CCOCC1)CCC)=O)Cl.S(C1C=CC(C)=CC=1)(=O)(=O)O
|
| InChi Key |
IIKVQQNZHGBYGQ-KNTRCKAVSA-N
|
| InChi Code |
InChI=1S/C25H28Cl2N4O3/c1-2-3-22(30-25(32)19(17-28)16-23-21(26)8-9-24(27)29-23)18-4-6-20(7-5-18)34-15-12-31-10-13-33-14-11-31/h4-9,16,22H,2-3,10-15H2,1H3,(H,30,32)/b19-16+
|
| Chemical Name |
(E)-2-cyano-3-(3,6-dichloropyridin-2-yl)-N-[1-[4-(2-morpholin-4-ylethoxy)phenyl]butyl]prop-2-enamide
|
| Synonyms |
EOAI-3402143 Tosylate EOAI 3402143 Tosylate EOAI 402143 Tosylate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~99.32 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.97 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. View More
Solubility in Formulation 3: 10 mg/mL (19.86 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4801 mL | 7.4006 mL | 14.8012 mL | |
| 5 mM | 0.2960 mL | 1.4801 mL | 2.9602 mL | |
| 10 mM | 0.1480 mL | 0.7401 mL | 1.4801 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
