Exisulind
Identification
- Generic Name
- Exisulind
- DrugBank Accession Number
- DB06246
- Background
Not Available
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 372.41
Monoisotopic: 372.083158364 - Chemical Formula
- C20H17FO4S
- Synonyms
- 5-Fluoro-2-methyl-1-((Z)-p-(methylsulfonyl)benzylidene)indene-3-acetic acid
- cis-5-Fluoro-2-methyl-1-(p-methylsulfonylbenzylidenyl)indene-3-acetic acid
- Exisulind
- Sulindac sulfone
- External IDs
- FGN 1
Pharmacology
- Indication
Investigated for use/treatment in adenomatous polyposis coli, lung cancer, prostate cancer, colon polyps, Barrett's esophagus disease, and pediatric indications.
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- Pharmacodynamics
Not Available
- Mechanism of action
Exisulind is a sulindac derivative of a class of compounds called selective apoptotic anti-neoplastic drugs (SAANDs), which inhibit the enzyme cyclic guanosine monophosphodiesterase (cGMP - PDE). Exisulind is specific for apoptotic effects in precancerous and cancerous colorectal cells due to their overexpression of cGMP. Sustained elevation of cGMP and protein kinase G (PKG) activation may be also implicated in the induction of apoptosis by Exisulind.
Target Actions Organism UGlutathione S-transferase P inhibitorHumans UAldose reductase inhibitorHumans UAldo-keto reductase family 1 member B10 inhibitorHumans UcAMP-specific 3',5'-cyclic phosphodiesterase 4D Not Available Humans UcAMP-specific 3',5'-cyclic phosphodiesterase 4C Not Available Humans UcGMP-specific 3',5'-cyclic phosphodiesterase Not Available Humans UcGMP-dependent 3',5'-cyclic phosphodiesterase Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Exisulind is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Exisulind is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Exisulind is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Exisulind is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Exisulind is combined with Bupivacaine. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Aptosyn (OSI Pharmaceuticals Inc.) / Prevatec (Cell Pathways Inc.)
Categories
- Drug Categories
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anticarcinogenic Agents
- Antineoplastic Agents
- Antirheumatic Agents
- Compounds used in a research, industrial, or household setting
- Cyclooxygenase Inhibitors
- Enzyme Inhibitors
- Indenes
- Peripheral Nervous System Agents
- Protective Agents
- Sensory System Agents
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- K619IIG2R9
- CAS number
- 59973-80-7
- InChI Key
- MVGSNCBCUWPVDA-MFOYZWKCSA-N
- InChI
- 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-
- IUPAC Name
- 2-[(1Z)-5-fluoro-1-[(4-methanesulfonylphenyl)methylidene]-2-methyl-1H-inden-3-yl]acetic acid
- SMILES
- CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(C=C1)S(C)(=O)=O
References
- General References
- Authors unspecified: Exisulind: Aptosyn, FGN 1, Prevatac, sulindac sulfone. Drugs R D. 2004;5(4):220-6. [Article]
- Piazza GA, Thompson WJ, Pamukcu R, Alila HW, Whitehead CM, Liu L, Fetter JR, Gresh WE Jr, Klein-Szanto AJ, Farnell DR, Eto I, Grubbs CJ: Exisulind, a novel proapoptotic drug, inhibits rat urinary bladder tumorigenesis. Cancer Res. 2001 May 15;61(10):3961-8. [Article]
- Thompson WJ, Piazza GA, Li H, Liu L, Fetter J, Zhu B, Sperl G, Ahnen D, Pamukcu R: Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta-catenin. Cancer Res. 2000 Jul 1;60(13):3338-42. [Article]
- External Links
- ChemSpider
- 4582441
- ChEBI
- 64212
- ChEMBL
- CHEMBL488025
- ZINC
- ZINC000012341529
- PDBe Ligand
- SLO
- Wikipedia
- Exisulind
- PDB Entries
- 3rx2
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 1 2 Completed Prevention Neoplasms of the Prostate 1 2 Completed Treatment Lung Cancer 2 2 Completed Treatment Neoplasms of the Prostate 1 2 Completed Treatment Prostate Cancer 3
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00155 mg/mL ALOGPS logP 2.94 ALOGPS logP 3.03 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 3.94 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 71.44 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 99.2 m3·mol-1 Chemaxon Polarizability 38.03 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00fr-0009000000-3d5f72edf1117eea67f2 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00b9-0009000000-2d3e0c221b2ae037e8eb Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-cb8831730b755c670f8a Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0abi-0009000000-a9a5282965f18a695524 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0abj-0596000000-0e6b8bf37dceb7ae7549 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9068000000-986ce28d79a2582d55e8 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 189.01503 predictedDeepCCS 1.0 (2019) [M+H]+ 191.37303 predictedDeepCCS 1.0 (2019) [M+Na]+ 197.46617 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- S-nitrosoglutathione binding
- Specific Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
- Gene Name
- GSTP1
- Uniprot ID
- P09211
- Uniprot Name
- Glutathione S-transferase P
- Molecular Weight
- 23355.625 Da
References
- Nobuoka A, Takayama T, Miyanishi K, Sato T, Takanashi K, Hayashi T, Kukitsu T, Sato Y, Takahashi M, Okamoto T, Matsunaga T, Kato J, Oda M, Azuma T, Niitsu Y: Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. Gastroenterology. 2004 Aug;127(2):428-43. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Glyceraldehyde oxidoreductase activity
- Specific Function
- Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
- Gene Name
- AKR1B1
- Uniprot ID
- P15121
- Uniprot Name
- Aldose reductase
- Molecular Weight
- 35853.125 Da
References
- Zheng X, Zhang L, Zhai J, Chen Y, Luo H, Hu X: The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase. FEBS Lett. 2012 Jan 2;586(1):55-9. doi: 10.1016/j.febslet.2011.11.023. Epub 2011 Dec 8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Retinal dehydrogenase activity
- Specific Function
- Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldeh...
- Gene Name
- AKR1B10
- Uniprot ID
- O60218
- Uniprot Name
- Aldo-keto reductase family 1 member B10
- Molecular Weight
- 36019.295 Da
References
- Cousido-Siah A, Ruiz FX, Crespo I, Porte S, Mitschler A, Pares X, Podjarny A, Farres J: Structural analysis of sulindac as an inhibitor of aldose reductase and AKR1B10. Chem Biol Interact. 2015 Jun 5;234:290-6. doi: 10.1016/j.cbi.2014.12.018. Epub 2014 Dec 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
- Gene Name
- PDE4D
- Uniprot ID
- Q08499
- Uniprot Name
- cAMP-specific 3',5'-cyclic phosphodiesterase 4D
- Molecular Weight
- 91114.1 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Metal ion binding
- Specific Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
- Gene Name
- PDE4C
- Uniprot ID
- Q08493
- Uniprot Name
- cAMP-specific 3',5'-cyclic phosphodiesterase 4C
- Molecular Weight
- 79900.795 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Metal ion binding
- Specific Function
- Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
- Gene Name
- PDE5A
- Uniprot ID
- O76074
- Uniprot Name
- cGMP-specific 3',5'-cyclic phosphodiesterase
- Molecular Weight
- 99984.14 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Tpr domain binding
- Specific Function
- Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.Isoform PDE2A2: Regulates Mit...
- Gene Name
- PDE2A
- Uniprot ID
- O00408
- Uniprot Name
- cGMP-dependent 3',5'-cyclic phosphodiesterase
- Molecular Weight
- 105715.85 Da
Drug created at March 19, 2008 16:19 / Updated at February 21, 2021 18:52