WS-384 is an orally active dual LSD1 and DCN1-UBC12 protein-protein interaction inhibitor with IC50 values of 338.79 nM and 14.81 nM, respectively. WS-384 has anticancer activity and can cause cell cycle arrest, DNA damage, and induction of apoptosis. WS-38 can be used in the study of non-small cell lung cancer (NSCLC).

Physicochemical Properties

Molecular Formula	C18H21BRCLN9S2
Molecular Weight	542.91
Appearance	Typically exists as solid at room temperature
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)

Biological Activity

Targets	IC50: 338.79 nM (LSD1)[1]. IC50: 14.81 nM (DCN1-UBC12 Protein-protein interaction)[1].
ln Vitro	WS-384 (1-32 μM; 24-72 h) inhibited the growth of A549 and H1975 cells in a time- and dose-dependent manner with IC50 values between 2.15 and 6.67 μM, showing anticancer activity [1]. WS-384 (1-8 μM; 48 h) increased the expression levels of p21 gene and protein in A549 and H1975 cells by inhibiting the ubiquitination modification of cullin 1 and reducing H3K4 demethylation at the CDKN1A promoter, thereby inducing cell cycle arrest at the G2/M phase and apoptosis. WS-384 (1-8 μM; 48 h) can also cause DNA damage [1]. Apoptosis Analysis[1] Cell Line: A549, H1975 Concentration: 1 μM, 2 μM, 4 μM, 8 μM (A549); 0.5 μM, 1 μM, 2 μM, 4 μM (H1975) Incubation Time: 48 h Result: Increased the apoptosis rate in a concentration-dependent manner, with the apoptosis rate of A549 cells reaching 44.9% at a concentration of 8 μM and the apoptosis rate of H1975 cells reaching 36.42% at a concentration of 4 μM.
ln Vivo	WS-384 (25-50 mg/kg; po; Once daily for 36 consecutive days) can effectively inhibit the growth of NSCLC tumors in the BALB/c nude mouse xenograft model with low toxicity [1].
Cell Assay	Western Blot Analysis[1] Cell Types: A549, H1975 Concentration: 2 μM, 4 μM, 8 μM (A549); 1 μM, 2 μM, 4 μM (H1975) Incubation Duration: 48 h Experimental Results: Blocked the neddylation of cullin1 and cullin3 but had no effect on the neddylation of other cullin members (cullin2, cullin4A, and cullin5). Increased the proteins expression of cleaved caspase 3, cleaved caspase 7, cleaved caspase 9, and cleaved PARP. Decreased the protein expression of p-CDC2, cyclin B1. CDK4 and CDK6. Increased the protein expression γ-H2AX (a marker protein of DNA damage).
Animal Protocol	Animal/Disease Models:BALB/c nude mice xenograft model[1]. Doses: 25 mg/kg; 50 mg/kg; Route of Administration: Oral gavage (p.o.); Once daily for 36 consecutive days Experimental Results: Significantly reduced tumor weight and volume in mice in the 50 mg/kg group. Had no significant toxic effects on the heart, liver, spleen, lungs, and kidneys.
References	[1]. Discovery of WS-384, a first-in-class dual LSD1 and DCN1-UBC12 protein-protein interaction inhibitor for the treatment of non-small cell lung cancer. Biomed Pharmacother. 2024;173:116240.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	1.8419 mL	9.2096 mL	18.4193 mL
	5 mM	0.3684 mL	1.8419 mL	3.6839 mL
	10 mM	0.1842 mL	0.9210 mL	1.8419 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.