| Size | Price | Stock | Qty |
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| 5mg |
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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. The compound's effects on cancer prevention and treatment are evaluated.
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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. The compound is stable under recommended storage conditions.
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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 when handling the compound.
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| References |
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| 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 (Sulindac Sulfone; CAS 59864-04-9) is 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 for research applications. |
| Molecular Formula |
C20H17O4FS
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|---|---|
| Molecular Weight |
372.40998
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| Exact Mass |
372.083
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| CAS # |
59864-04-9
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| PubChem CID |
5472495
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
601.9±55.0 °C at 760 mmHg
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| Flash Point |
317.8±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.620
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| LogP |
3.54
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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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| 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 (~268.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.69 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (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.
Link: https://clinicaltrials.gov/ct2/show/NCT00041314
Conditions:Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT00283803
Conditions:Prostate CancerLink: https://clinicaltrials.gov/ct2/show/NCT00041054
Conditions:Lung Cancer
Title:Docetaxel, Estramustine, and Exisulind in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy
Status:Completed
updateDate:2016-07-01
Ctid:NCT00052845
Link: https://clinicaltrials.gov/ct2/show/NCT00052845
Conditions:Prostate CancerLink: https://clinicaltrials.gov/ct2/show/NCT00026468
Conditions:Colorectal Cancer|Small Intestine CancerLink: https://clinicaltrials.gov/ct2/show/NCT00078910
Conditions:Prostate CancerLink: https://clinicaltrials.gov/ct2/show/NCT00037609
Conditions:Breast Neoplasms|Metastases, NeoplasmLink: https://clinicaltrials.gov/ct2/show/NCT00072618
Conditions:NSCLCLink: https://clinicaltrials.gov/ct2/show/NCT00085826
Conditions:Non-Small Cell Lung CancerLink: https://clinicaltrials.gov/ct2/show/NCT00166478
Conditions:Prostatic NeoplasmsLink: https://clinicaltrials.gov/ct2/show/NCT00166426
Conditions:Prostatic NeoplasmsProducts are for research use only; We do not sell to patients
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