| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
|
Purity: ≥98%
MSAB is a novel and potent inhibitor of Wnt/β-catenin signaling with anticancer activity. It acts by binding to β-catenin, promoting its degradation, and specifically downregulating Wnt/β-catenin target genes. The Wnt/β-catenin signaling pathway plays a major role in tissue homeostasis, and its dysregulation can lead to various human diseases. Aberrant activation of β-catenin is oncogenic and is a critical driver in the development and progression of human cancers.
| Targets |
Wnt/β-catenin
|
|---|---|
| ln Vitro |
MSAB (2-10 μM) specifically lowers Wnt-dependent cells' survival while having minimal effect on Wnt-independent cells and healthy human cells [1]. T cell factor (TCF) luciferase reporter activity in HCT116 cells is inhibited by MSAB (0.01-10 μM; 20 hours) [1]. In HEK293T cells, Wnt3a-induced elevations in TOP-Luc activation and active β-catenin levels are inhibited by MSAB (20 hours) [1]. In HCT116 cells, MSAB (0.5-10 μM; 20 hours) lowers the levels of endogenous Wnt target gene mRNA and protein [1]. Protease-dependent MSAB (5 μM) stimulates β-catenin degradation in HCT116 cells for 16 hours [1].
|
| ln Vivo |
In a mouse xenograft model, MSAB (10–20 mg/kg; daily intraperitoneal injection for 2 weeks) reduces the formation of tumors in Wnt-dependent cancer cells [1]. In MMTV-Wnt1 transgenic mice, MSAB (10–20 mg/kg; intraperitoneally given twice daily for two weeks) suppresses tumor growth [1].
|
| Enzyme Assay |
High throughput chemical screening was performed as previously described (Raj et al., 2011; Stanton et al., 2009) with modifications. For screening of inhibitors targeting Wnt/β-catenin signaling pathway, HCT116-TOP cells (HCT116 cells stably transfected with TOPFLASH (TCF/LEF1-optimized promoter)-firefly luciferase reporter) were seeded using automated plate filler in 384-well plates and incubated at 37°C overnight. Next day, each small molecule compound was pin-transferred to each plate. Plates were covered with lids and incubated at 37°C for 20 h. The following day, assa y plates were allowed to equilibrate to room temperature for 10 min. Luciferase assay reagent was added to each well, incubated for 15 min, then read using a Perkin Elmer Envision luminometer to quantitate luciferase levels. Compounds that decrease luciferase activity were selected as hits. Luciferase values were normalized to the positive and negative controls to determine a normalized percent inhibition. Based on the normalized luciferase values, compounds showing >50% inhibition in both replicates compared to DMSO control were considered as active compounds. All small molecules were tested in duplicates[1].
|
| Cell Assay |
Cell viability assay [1]
Cell viability was assayed by Sulforhodamine B based In Vitro Toxicology Assay Kit. Cells were plated in 6-well plates, and after reaching 60-70% confluency, the cells were treated with chemicals at concentrations and durations as indicated in the figures and figure legends. Staining and quantitative analysis were performed according to the manufacturer’s manual. All experiments were performed as duplicates. Luciferase reporter assays[1] To measure transcriptional activity of Wnt, NF-κB, iNOS, or NOTCH, we transiently transfected HCT116 cells or HEK293T cells with TOP-FLASH, FOP-FLASH, NF-κB, iNOS, or NOTCH luciferase reporter, along with an internal Renilla luciferase reporter plasmid as a control (hRL-null). Transfection was performed with lipofectamine 2000 according to the manufacturer’s protocol. Luciferase activity was measured with the Dual Luciferase Reporter Assay System as according to the manufacturer’s manual. The results were normalized to the control Renilla activity. The reported data represent the average of three independent experiments. |
| Animal Protocol |
Animal/Disease Models: Athymic nude mice (5-6 weeks) injected with HCT116, HT115, H23 or H460 cells [1]
Doses: 10, 20 mg/kg Route of Administration: Daily intraperitoneal (ip) injection for 2 weeks Experimental Results: Various mice The size and weight are diminished in Wnt-dependent manner in HCT116, HT115, and H23 tumor types. For xenograft tumor models, cancer cell line HCT116, HT115, H23, or H460 (2x 106) was injected subcutaneously (s.c.) into the flanks of athymic nude mice (NCr nude, 5-6 week old). We also used MMTV-Wnt1 transgenic mice. About 15% of these mice develop mammary tumors between 6 weeks and 3 months of age in MMTV-Wnt1 transgenic mice model. Tumors were allowed to grow to 40 mm3 prior to intraperitoneal injection. One week after cellular inoculation, mice were treated by intraperitoneal injection with vehicle or MSAB (10 or 20 mg/kg) every day for two weeks. Two weeks after intraperitoneal injection, the mice were euthanized and tumor weight was measured. Tumor dimensions were measured, and volume was calculated by length (L) and width (W) using the formula (volume = π/6 x L x W2).[1] |
| References | |
| Additional Infomation |
The Wnt/β-catenin signaling pathway plays a major role in tissue homeostasis, and its dysregulation can lead to various human diseases. Aberrant activation of β-catenin is oncogenic and is a critical driver in the development and progression of human cancers. Despite the significant potential of targeting the oncogenic β-catenin pathway for cancer therapy, the development of specific inhibitors remains insufficient. Using a T cell factor (TCF)-dependent luciferase-reporter system, we screened for small-molecule compounds that act against Wnt/β-catenin signaling and identified MSAB (methyl 3-{[(4-methylphenyl)sulfonyl]amino}benzoate) as a selective inhibitor of Wnt/β-catenin signaling. MSAB shows potent anti-tumor effects selectively on Wnt-dependent cancer cells in vitro and in mouse cancer models. MSAB binds to β-catenin, promoting its degradation, and specifically downregulates Wnt/β-catenin target genes. Our findings might represent an effective therapeutic strategy for cancers addicted to the Wnt/β-catenin signaling pathway.[1]
|
| Molecular Formula |
C15H15NO4S
|
|---|---|
| Molecular Weight |
305.3489
|
| Exact Mass |
305.072
|
| Elemental Analysis |
C, 59.00; H, 4.95; N, 4.59; O, 20.96; S, 10.50
|
| CAS # |
173436-66-3
|
| PubChem CID |
1159052
|
| Appearance |
Typically exists as white to off-white solids at room temperature
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
456.5±55.0 °C at 760 mmHg
|
| Melting Point |
152-154°C
|
| Flash Point |
229.9±31.5 °C
|
| Vapour Pressure |
0.0±1.1 mmHg at 25°C
|
| Index of Refraction |
1.600
|
| LogP |
1.04
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
21
|
| Complexity |
449
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC=C(C=C1)S(=O)(=O)NC2=CC=CC(=C2)C(=O)OC
|
| InChi Key |
CVKBYFCJQSPBOI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H15NO4S/c1-11-6-8-14(9-7-11)21(18,19)16-13-5-3-4-12(10-13)15(17)20-2/h3-10,16H,1-2H3
|
| Chemical Name |
methyl 3-[(4-methylphenyl)sulfonylamino]benzoate
|
| Synonyms |
METHYL 3-(4-METHYLBENZENESULFONAMIDO)BENZOATE; methyl 3-{[(4-methylphenyl)sulfonyl]amino}benzoate; MSAB?; CHEMBL5189621; SCHEMBL16116948; EX-A4298;
|
| 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 : ~250 mg/mL (~818.73 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.81 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 20.8 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: ≥ 2.08 mg/mL (6.81 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2749 mL | 16.3747 mL | 32.7493 mL | |
| 5 mM | 0.6550 mL | 3.2749 mL | 6.5499 mL | |
| 10 mM | 0.3275 mL | 1.6375 mL | 3.2749 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
COA