| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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| Targets |
β-catenin/BCL9 complex
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|---|---|
| ln Vitro |
Top hits identified by HTS (table S1) that were commercially available were purchased and examined with a 10-dose response AlphaScreen assay, in which compounds were titrated against full-length β-catenin and against an unrelated protein (BRD9) as a counter-screen to further filter out any unspecific compounds (Fig. 1F). This assay validated 16 compounds that specifically and competitively inhibited β-catenin/BCL9, but not BRD9/ligand complexes. The five top-performing compounds include E722-2648 (C-1), L814-1428 (C-2), SYN22094413 (C-3), L859-1770 (C-4), and F838-0143 (C-5) and will be referred to using their shortened names (C-1 to C-5) throughout this manuscript (Fig. 1F). To further confirm specificity and characterize the binding thermodynamics of the top 16 compounds, we used isothermal titration calorimetry (ITC). Dissociation constant (KD) values for the five top-performing compounds ranged between 0.27 and 2.22 μM and were comparable to the BCL9 peptide used as a positive control (2.74 μM) (Fig. 1G and table S2).[1]
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| References | |
| Additional Infomation |
Dysregulated Wnt/β-catenin signaling is implicated in the pathogenesis of many human cancers, including colorectal cancer (CRC), making it an attractive clinical target. With the aim of inhibiting oncogenic Wnt activity, we developed a high-throughput screening AlphaScreen assay to identify selective small-molecule inhibitors of the interaction between β-catenin and its coactivator BCL9. We identified a compound that consistently bound to β-catenin and specifically inhibited in vivo native β-catenin/BCL9 complex formation in CRC cell lines. This compound inhibited Wnt activity, down-regulated expression of the Wnt/β-catenin signature in gene expression studies, disrupted cholesterol homeostasis, and significantly reduced the proliferation of CRC cell lines and tumor growth in a xenograft mouse model of CRC. This study has therefore identified a specific small-molecule inhibitor of oncogenic Wnt signaling, which may have value as a probe for functional studies and has important implications for the development of novel therapies in patients with CRC.[1]
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| Molecular Formula |
C21H30N2OS2
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|---|---|
| Molecular Weight |
390.605702877045
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| Exact Mass |
390.179
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| CAS # |
931963-55-2
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| PubChem CID |
20913345
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
538
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C2C=C(C(NCCCN3CCCC(C)C3)=O)SCC=2C2=C1CCCC2
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| InChi Key |
KTLYLDMTGYBKTC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H30N2OS2/c1-15-6-4-10-23(13-15)11-5-9-22-21(24)20-12-19-17(14-25-20)16-7-2-3-8-18(16)26-19/h12,15H,2-11,13-14H2,1H3,(H,22,24)
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| Chemical Name |
N-[3-(3-methylpiperidin-1-yl)propyl]-6,7,8,9-tetrahydro-1H-thiopyrano[4,3-b][1]benzothiole-3-carboxamide
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| Synonyms |
E722-2648; CHEMBL5398378; 931963-55-2; N-[3-(3-METHYL-1-PIPERIDINYL)PROPYL]-6,7,8,9-TETRAHYDRO-1H-THIOPYRANO[4,3-B][1]BENZOTHIOPHENE-3-CARBOXAMIDE; N-[3-(3-methylpiperidin-1-yl)propyl]-6,7,8,9-tetrahydro-1H-thiopyrano[4,3-b][1]benzothiole-3-carboxamide;
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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) |
Typically soluble in DMSO (e.g. 10 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 | 2.5601 mL | 12.8005 mL | 25.6010 mL | |
| 5 mM | 0.5120 mL | 2.5601 mL | 5.1202 mL | |
| 10 mM | 0.2560 mL | 1.2800 mL | 2.5601 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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