WS-383 is a potent, selective, reversible inhibitor of DCN1-UBC12 interaction with IC50 of 11 nM. WS-383 inhibits the ubiquitin-like modification of Cul3/1, causing the accumulation of p21, p27 and NRF2.

Physicochemical Properties

Molecular Formula	C18H21CL2N9S2
Molecular Weight	498.455636739731
Exact Mass	497.073
CAS #	2247544-02-9
Related CAS #	WS-383 free base;2247543-65-1
PubChem CID	138319703
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	8
Heavy Atom Count	31
Complexity	540
Defined Atom Stereocenter Count	0
SMILES	ClC1C=CC(=CC=1)CSC1N=C2N=C(C)C=C(N2N=1)SC1=NN=NN1CCN(C)C.Cl
InChi Key	LJZUAAKUJAXXHQ-UHFFFAOYSA-N
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
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
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 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)

Biological Activity

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].
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.
References	[1]. Development of Highly Potent, Selective, and Cellular Active Triazolo[1,5- a]pyrimidine-Based Inhibitors Targeting the DCN1-UBC12 Protein-Protein Interaction. J Med Chem. 2019 Mar 14;62(5):2772-2797.

Solubility Data

Solubility (In Vitro)

DMSO : ~7.35 mg/mL (~14.75 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.