| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| Targets |
(E/Z)-Sulindac sulfide has multiple targets. It is a non-competitive inhibitor of gamma-secretase with an IC50 of 20.2 μM. As a γ-secretase modulator (GSM), it selectively alters the enzyme's cleavage pattern to reduce Aβ42 production. It also inhibits COX-1 (ID50 = 0.5 µM) and COX-2 (ID50 = 14 µM), inhibits aldose reductase (IC50 = 279 nM), and inhibits Ras signaling and NF-κB.
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|---|---|
| ln Vitro |
In vitro, (E/Z)-Sulindac sulfide inhibits the growth of and induces apoptosis in prostate cancer cell lines. It inhibits the growth of colorectal carcinoma cells, such as HCA-7 and HCT-116, and reduces prostaglandin E2 production. As a GSM, it reduces Aβ42 production in favor of shorter Aβ species. It also inhibits aldose reductase activity.
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| ln Vivo |
In vivo, animal studies have shown that sulindac sulfide inhibits the growth of HCA-7 xenografts in mice. It is the active metabolite responsible for the anti-inflammatory and tumor-suppressive effects of its parent drug, sulindac. Its activity as a GSM also suggests potential in vivo effects on amyloid-beta metabolism in the brain.
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| Enzyme Assay |
Non-cellular assays for (E/Z)-Sulindac sulfide include gamma-secretase activity assays. These assays typically use purified or partially purified gamma-secretase enzyme complexes incubated with a fluorogenic substrate that mimics the cleavage site of APP. The enzyme's activity is measured by the increase in fluorescence upon cleavage. The compound's inhibitory effect (IC50) is determined. Similar assays can be performed to measure its inhibition of COX-1, COX-2, or aldose reductase using the respective purified enzymes and substrates.
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| Cell Assay |
In vitro cellular assays for (E/Z)-Sulindac sulfide often use cancer cell lines like HCA-7 or HCT-116 to study its anti-proliferative and pro-apoptotic effects. Cells are treated with the compound, and cell viability is measured using assays like MTT. Apoptosis is assessed via methods like Annexin V staining. To study its GSM activity, cells (e.g., CHO cells) that overexpress APP are treated with the compound, and the levels of Aβ40 and Aβ42 peptides in the culture medium are measured by ELISA.
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| Animal Protocol |
In vivo animal studies for sulindac sulfide typically use xenograft mouse models. For example, HCA-7 or HCT-116 tumor cells are implanted subcutaneously in mice. Once tumors are established, the animals are treated with sulindac sulfide, and tumor growth is monitored over time. Endpoints include tumor volume, weight, and analysis of proliferation and apoptosis markers in the tumor tissue.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of (E/Z)-Sulindac sulfide are known from its role as the active metabolite of sulindac. Sulindac is a prodrug that is converted to the active sulfide metabolite in the body. This sulfide is responsible for the drug's pharmacological effects. Its parent compound, sulindac, is clinically used and has well-characterized oral bioavailability and metabolism.
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| Toxicity/Toxicokinetics |
The toxicity profile of (E/Z)-Sulindac sulfide is related to its parent compound, sulindac. Sulindac is generally well-tolerated but can cause gastrointestinal side effects (e.g., ulceration, bleeding) typical of NSAIDs. Its use is contraindicated in patients with a history of NSAID hypersensitivity. As a research compound, it should be handled with standard laboratory precautions.
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| References | |
| Additional Infomation |
Sulindac sulfide is an aryl sulfide and a metabolite of sulindac. Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) with anticancer activity. It functions as an NSAID, an apoptosis inducer, and an antitumor drug. Sulindac sulfide is an aryl sulfide, an organofluorine compound, and a monocarboxylic acid. It is functionally related to sulindac. Sulindac sulfide is the active metabolite of sulindac, a sulfinyl indene derivative with anti-inflammatory, analgesic, and antipyretic effects. Sulindac is a NSAID that works by inhibiting the cyclooxygenase (COX-1 and COX-2)-mediated conversion of arachidonic acid to pro-inflammatory prostaglandins. This drug may have a chemopreventive effect against colorectal cancer through a mechanism of inducing apoptosis. The sulfide metabolite is excreted via bile and reabsorbed by the intestine, thus helping to maintain stable blood concentrations and reduce gastrointestinal side effects. (NCI04)
(E/Z)-Sulindac sulfide is a research-grade compound for laboratory use only and is not a clinical therapeutic itself, though its parent drug sulindac is FDA-approved for treating arthritis and other inflammatory conditions. Its primary research applications are in Alzheimer's disease (as a GSM) and cancer research (as a COX inhibitor and apoptosis inducer). Its CAS number is 32004-67-4, and its molecular formula is C₂₀H₁₇FO₂S. |
| Molecular Formula |
C20H17O2FS
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|---|---|
| Molecular Weight |
340.41118
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| Exact Mass |
340.093
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| CAS # |
32004-67-4
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| Related CAS # |
Sulindac sulfide;49627-27-2
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| PubChem CID |
5352624
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| Appearance |
Yellow to orange solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
526.3±50.0 °C at 760 mmHg
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| Melting Point |
189-191°C
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| Flash Point |
272.1±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.653
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| LogP |
5.74
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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 |
4
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| Heavy Atom Count |
24
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| Complexity |
546
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC\1=C(C2=C(/C1=C\C3=CC=C(C=C3)SC)C=CC(=C2)F)CC(=O)O
|
| InChi Key |
LFWHFZJPXXOYNR-MFOYZWKCSA-N
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| InChi Code |
InChI=1S/C20H17FO2S/c1-12-17(9-13-3-6-15(24-2)7-4-13)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-
|
| Chemical Name |
2-[(3Z)-6-fluoro-2-methyl-3-[(4-methylsulfanylphenyl)methylidene]inden-1-yl]acetic acid
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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) |
DMSO: ≥ 100 mg/mL (~293.8 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9376 mL | 14.6882 mL | 29.3763 mL | |
| 5 mM | 0.5875 mL | 2.9376 mL | 5.8753 mL | |
| 10 mM | 0.2938 mL | 1.4688 mL | 2.9376 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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