| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
DCN1 (defective in cullin neddylation 1) and UBC12 (ubiquitin-conjugating enzyme E2 M). WS-383 inhibits the DCN1-UBC12 interaction, preventing the transfer of NEDD8 from UBC12 to cullin proteins. This inhibits cullin-RING ligase (CRL) activity, leading to the stabilization of CRL substrates including p21, p27, and NRF2.
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| ln Vitro |
WS-383 (10 μM) uses staurosporine and BIBW 2992 as positive controls and targets a panel of kinases, including BTK, CDK, and EGFR [L858R]. At 10.0 μM, WS-383 demonstrates modest inhibitory effect and is specific to the DCN1-UBC12 interaction rather than other kinases [1]. While WS-383 (0.03-3 μM; 24 hours) is unsuccessful in suppressing the neddylation of other cullin members, it prevents Cul3 neddylation at 3 μM and also has a little inhibitory effect on Cul1 neddylation at 10 μM [1]. The SCF E3 complex is formed by the addition of WS-383 (0.03-3 μM; 24 hours) to Cul1, Skp1 (adapter protein), F-box proteins, and RBX1/RBX2 RING proteins. Dose-dependent expression of cyclin-dependent kinase inhibitors 1A (p21) and 1B (p27) is observed in MGC-803 and KYSE70 [1].
WS-383 inhibits DCN1-UBC12 interaction with an IC₅0 of 11 nM. The compound is selective for DCN1 over other neddylation pathway components. Inhibition of Cul3/1 neddylation leads to accumulation of p21, p27, and NRF2 proteins. p21 and p27 are cell cycle inhibitors that cause G1 arrest, while NRF2 activates antioxidant and cytoprotective genes. |
| ln Vivo |
In vivo, WS-383 would be expected to induce accumulation of p21, p27, and NRF2 in tissues. This could lead to cell cycle arrest and enhanced antioxidant responses. The compound may have potential applications in cancer (by inducing cell cycle arrest) and in diseases where NRF2 activation is beneficial (e.g., neurodegenerative diseases, inflammation).
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| Enzyme Assay |
DCN1-UBC12 interaction assays typically employ AlphaScreen, TR-FRET, or ELISA-based formats. Biotinylated DCN1 peptide or protein is incubated with UBC12 and test compound. The interaction is detected using labeled antibodies or beads, and IC₅0 values are calculated from competition curves. Neddylation assays measure the transfer of NEDD8 to cullin proteins using recombinant components.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MGC-803 Cell Tested Concentrations: 0.03 μM; 0.3μM; 3μM; 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: N8-Cul1 and N8-Cul2 protein expression was diminished. Western Blot Analysis [1] Cell Types: MGC-803 and KYSE70 cells Tested Concentrations: 0.03 μM; 0.3μM; 3μM; 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced the accumulation of p21, p27 and NRF2 in MGC-803 cells. Cells (e.g., HEK293T or cancer cell lines) are treated with WS-383 at various concentrations for 4-24 hours. Cullin neddylation is assessed by Western blotting using antibodies that distinguish neddylated from non-neddylated cullins. p21, p27, and NRF2 protein levels are measured by Western blotting. Cell cycle analysis is performed by flow cytometry to assess G1 arrest. |
| Animal Protocol |
C57BL/6 mice or other rodent models are administered WS-383 via intraperitoneal injection or oral gavage. Tissues (liver, spleen, kidney, tumor) are harvested at various time points. Cullin neddylation and substrate accumulation (p21, p27, NRF2) are assessed by Western blotting. Pharmacodynamic effects and compound exposure are correlated to determine target engagement.
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| ADME/Pharmacokinetics |
WS-383 has a molecular weight of 498.46 g/mol and formula C1₈H21Cl2N₉S2. Standard PK parameters (half-life, Cmax, AUC, clearance, volume of distribution, oral bioavailability) would be determined in rodent PK studies following IV and PO administration. The compound is soluble in DMSO and formulated in suitable vehicles for in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicology data for WS-383 are not publicly available. Standard preclinical safety assessment would include cytotoxicity assays, hERG channel inhibition testing, and repeat-dose toxicology studies in rodents. Given the role of neddylation in normal cellular physiology, potential toxicities related to off-target effects or excessive pathway inhibition would be evaluated.
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| References | |
| Additional Infomation |
WS-383 is a research compound for studying the neddylation pathway. It is not clinically approved. The compound is useful for investigating the roles of cullin-RING ligases and their substrates (p21, p27, NRF2) in cell cycle regulation, cancer, and oxidative stress responses. WS-383 serves as a tool for validating DCN1 as a therapeutic target.
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| Molecular Formula |
C18H21CL2N9S2
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|---|---|
| Molecular Weight |
498.455636739731
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| Exact Mass |
497.073
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| CAS # |
2247544-02-9
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| Related CAS # |
WS-383 free base;2247543-65-1
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| PubChem CID |
138319703
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
540
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1)CSC1N=C2N=C(C)C=C(N2N=1)SC1=NN=NN1CCN(C)C.Cl
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| InChi Key |
LJZUAAKUJAXXHQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H20ClN9S2.ClH/c1-12-10-15(30-18-22-24-25-27(18)9-8-26(2)3)28-16(20-12)21-17(23-28)29-11-13-4-6-14(19)7-5-13;/h4-7,10H,8-9,11H2,1-3H3;1H
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| Chemical Name |
2-[5-[[2-[(4-chlorophenyl)methylsulfanyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl]sulfanyl]tetrazol-1-yl]-N,N-dimethylethanamine;hydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~7.35 mg/mL (~14.75 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0062 mL | 10.0309 mL | 20.0618 mL | |
| 5 mM | 0.4012 mL | 2.0062 mL | 4.0124 mL | |
| 10 mM | 0.2006 mL | 1.0031 mL | 2.0062 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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