This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Exisulind
Accession Number
DB06246
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • FGN 1
  • sulindac sulfone
International/Other Brands
Aptosyn (OSI Pharmaceuticals Inc.) / Prevetac (Cell Pathways Inc.)
Categories
UNII
K619IIG2R9
CAS number
59973-80-7
Weight
Average: 372.41
Monoisotopic: 372.083158364
Chemical Formula
C20H17FO4S
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

Pharmacology

Indication

Investigated for use/treatment in adenomatous polyposis coli, lung cancer, prostate cancer, colon polyps, Barrett's esophagus disease, and pediatric indications.

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.

TargetActionsOrganism
UcAMP-specific 3',5'-cyclic phosphodiesterase 4DNot AvailableHuman
UcAMP-specific 3',5'-cyclic phosphodiesterase 4CNot AvailableHuman
UcGMP-specific 3',5'-cyclic phosphodiesteraseNot AvailableHuman
UcGMP-dependent 3',5'-cyclic phosphodiesteraseNot AvailableHuman
UGlutathione S-transferase P
inhibitor
Human
UAldose reductase
inhibitor
Human
UAldo-keto reductase family 1 member B10
inhibitor
Human
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Authors unspecified: Exisulind: Aptosyn, FGN 1, Prevatac, sulindac sulfone. Drugs R D. 2004;5(4):220-6. [PubMed:15230629]
  2. 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. [PubMed:11358813]
  3. 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. [PubMed:10910034]
External Links
ChemSpider
4582441
ChEBI
64212
ChEMBL
CHEMBL488025
HET
SLO
Wikipedia
Exisulind
PDB Entries
3rx2

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentNeoplasm Metastases / Neoplasms, Breast1
2CompletedPreventionProstatic Neoplasms1
2CompletedTreatmentLung Cancers2
2CompletedTreatmentProstate Cancer3
2CompletedTreatmentProstatic Neoplasms1
2, 3WithdrawnPreventionColorectal Cancers / Small Intestine Cancer1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1

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
PropertyValueSource
Water Solubility0.00155 mg/mLALOGPS
logP2.94ALOGPS
logP3.03ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)3.94ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.44 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity99.2 m3·mol-1ChemAxon
Polarizability38.03 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
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
Human
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
Human
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
Human
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
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:15300575]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:22155003]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:25532697]

Drug created on March 19, 2008 10:19 / Updated on November 02, 2018 06:15