| Size | Price | Stock | Qty |
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| 10mg |
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| 100mg |
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| 500mg |
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| Targets |
Exisulind exerts its effects through multiple mechanisms. It inhibits the enzyme cyclic guanosine monophosphate phosphodiesterase type 5 (PDE5), leading to sustained elevation of cGMP and activation of protein kinase G (PKG). This pathway induces apoptosis in cancer cells without inhibiting COX-1 or COX-2. Exisulind also inhibits aldose reductase with an IC₅₀ of 367 nM and inhibits the mTORC1 pathway by directly targeting voltage-dependent anion channel 1 and 2. The compound decreases NF-κB-mediated transcription.
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| ln Vitro |
In vitro, exisulind inhibits aldose reductase with an IC₅₀ of 367 nM. The compound induces apoptosis in human cancer cell lines. Exisulind inhibits invasion of breast cancer cells and colon cancer cells by decreasing NF-κB-mediated transcription of several miRNAs. The compound downregulates expression of STAT3 and survivin and decreases cell proliferation. Exisulind inhibits the mTORC1 pathway in colon cancer cells by targeting VDAC1 and VDAC2.
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| ln Vivo |
In vivo, exisulind has demonstrated efficacy in mouse models of cancer. The compound inhibits polyp formation and reduces COX-2 protein expression in colon tissues. Exisulind's pro-apoptotic effects through PDE5 inhibition and cGMP/PKG pathway activation contribute to its anti-cancer activity. The compound has been studied in clinical trials for the prevention of colorectal adenomas and the treatment of various cancers.
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| Enzyme Assay |
Non-cellular enzyme assays for exisulind involve assessing its inhibition of PDE5 using purified recombinant PDE5 enzyme. The enzyme is incubated with [³H]-cGMP as substrate in the presence of varying concentrations of exisulind. The hydrolysis of cGMP is measured by scintillation counting after separation of substrate from product. IC₅₀ values for PDE5 inhibition are determined from dose-response curves. Aldose reductase inhibition is assessed using a spectrophotometric assay with DL-glyceraldehyde as substrate.
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| Cell Assay |
In vitro cellular assays for exisulind involve treating cancer cell lines with the compound and assessing cell viability, apoptosis, and signaling pathways. Cell viability is measured using MTT or CellTiter-Glo® assays. Apoptosis is assessed by flow cytometry using Annexin V/PI staining or by measuring caspase activity. cGMP levels are quantified by ELISA. NF-κB activity is measured using reporter gene assays or by Western blotting for nuclear p65. mTORC1 pathway activity is assessed by Western blotting for phosphorylated S6K and 4E-BP1.
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| Animal Protocol |
In vivo animal experiments with exisulind are conducted in mouse models of colorectal cancer and other malignancies. Mice with APC mutations (Min mice) or xenografted tumors are treated with exisulind via oral gavage. Polyp or tumor number and size are measured. COX-2 expression and apoptosis markers are assessed in tissues by immunohistochemistry. Pharmacokinetic studies characterize absorption and tissue distribution.
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| ADME/Pharmacokinetics |
Exisulind has a molecular weight of 372.41 and a molecular formula of C₂₀H₁₇FO₄S. It is a solid at room temperature with a purity of ≥96%. The compound is soluble in DMSO and other organic solvents. It is typically stored at -20°C, protected from light and moisture. Exisulind is orally bioavailable and has been studied in clinical trials at doses of 200-400 mg twice daily.
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| Toxicity/Toxicokinetics |
Exisulind is generally well-tolerated at therapeutic doses. Unlike its parent compound sulindac, exisulind does not inhibit COX-1 or COX-2, resulting in a reduced risk of gastrointestinal ulceration. Common side effects include gastrointestinal disturbances. The compound should be used with caution in patients with renal or hepatic impairment. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
Sulindac sulfone is a sulfone metabolite of sulindac. It inhibits cell growth by inducing apoptosis, and this effect is independent of cyclooxygenase inhibition. It can inhibit the development and regression of precancerous adenomatous polyps. Sulindac sulfone is a lipoxygenase and COX-2 inhibitor. It has the effects of cyclooxygenase 2 inhibitor, EC 1.13.11.34 (arachidonic acid 5-lipoxygenase) inhibitor, and apoptosis inducer. It is a sulfone compound, a monocarboxylic acid, and an organofluorine compound. Its function is related to sulindac. Exisulin is an inactive metabolite of sulindac (a nonsteroidal anti-inflammatory drug). After oral administration, sulindac undergoes extensive biotransformation, including irreversible oxidation to sulindac sulfone. Approximately half of the administered dose of sulindac is excreted in the urine, primarily as a conjugated sulfone metabolite. (NCI04)
Drug Indications It has been studied for the treatment of adenomatous polyposis, lung cancer, prostate cancer, colonic polyps, Barrett's esophagus, and pediatric diseases. Mechanism of Action Exisulind is a derivative of sulindac and belongs to the class of selective apoptotic antitumor drugs (SAANDs). It inhibits cyclic guanosine monophosphate esterase (cGMP-PDE). Due to the overexpression of cGMP in precancerous and cancerous colorectal cells, exisulind has a specific apoptotic effect on these cells. The persistently elevated cGMP and protein kinase G (PKG) activation may also be related to exisulind-induced apoptosis. Exisulind (CAS 59973-80-7) is an alternative CAS number for sulindac sulfone, a selective apoptotic anti-neoplastic drug that inhibits PDE5. It induces apoptosis through cGMP/PKG pathway activation and inhibits aldose reductase (IC₅₀ = 367 nM). Exisulind has been studied for cancer prevention and treatment. The compound is available from various commercial suppliers. |
| Molecular Formula |
C20H17O4FS
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|---|---|
| Molecular Weight |
372.40998
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| Exact Mass |
372.083
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| CAS # |
59973-80-7
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| Related CAS # |
Sulindac;38194-50-2;Sulindac sulfone-d3;250608-67-4
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| PubChem CID |
5472495
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| Appearance |
Light yellow to yellow solid powder
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| Melting Point |
248-250ºC
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| LogP |
5.112
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
723
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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)S(=O)(=O)C)C=CC(=C2)F)CC(=O)O
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| InChi Key |
MVGSNCBCUWPVDA-MFOYZWKCSA-N
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| InChi Code |
InChI=1S/C20H17FO4S/c1-12-17(9-13-3-6-15(7-4-13)26(2,24)25)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-
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| Chemical Name |
2-[(3Z)-6-fluoro-2-methyl-3-[(4-methylsulfonylphenyl)methylidene]inden-1-yl]acetic acid
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| Synonyms |
CP248; Sulindac sulfone; Exisulind
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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) |
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
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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 | 2.6852 mL | 13.4261 mL | 26.8521 mL | |
| 5 mM | 0.5370 mL | 2.6852 mL | 5.3704 mL | |
| 10 mM | 0.2685 mL | 1.3426 mL | 2.6852 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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