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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Contraindications & Blackbox Warnings

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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
AcGMP-specific 3',5'-cyclic phosphodiesterase	modulator	Humans
UGlutathione S-transferase P	inhibitor	Humans
UAldo-keto reductase family 1 member B1	inhibitor	Humans
UAldo-keto reductase family 1 member B10	inhibitor	Humans
U3',5'-cyclic-AMP phosphodiesterase 4D	Not Available	Humans
U3',5'-cyclic-AMP phosphodiesterase 4C	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

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Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

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
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Ambroxol	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

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International/Other Brands: Aptosyn (OSI Pharmaceuticals Inc.) / Prevatec (Cell Pathways Inc.)

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

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Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
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3	Completed	Treatment	Non-Small Cell Lung Cancer (NSCLC)	1	somestatus	stop reason	just information to hide
2	Completed	Prevention	Neoplasms of the Prostate	1	somestatus	stop reason	just information to hide
2	Completed	Treatment	Lung Cancer	2	somestatus	stop reason	just information to hide
2	Completed	Treatment	Neoplasms of the Prostate	1	somestatus	stop reason	just information to hide
2	Completed	Treatment	Prostate Cancer	3	somestatus	stop reason	just information to hide

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	predicted	DeepCCS 1.0 (2019)
[M+H]+	191.37303	predicted	DeepCCS 1.0 (2019)
[M+Na]+	197.46617	predicted	DeepCCS 1.0 (2019)

Targets

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Details1. cGMP-specific 3',5'-cyclic phosphodiesterase

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Modulator

General 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:15489334, PubMed:9714779). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334)
Specific Function: 3',5'-cyclic-amp phosphodiesterase activity
Gene Name: PDE5A
Uniprot ID: O76074
Uniprot Name: cGMP-specific 3',5'-cyclic phosphodiesterase
Molecular Weight: 99984.14 Da

References

Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Details2. Glutathione S-transferase P

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Negatively regulates CDK5 activity via p25/p35 translocation to prevent neurodegeneration
Specific Function: Dinitrosyl-iron complex binding
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]

Details3. Aldo-keto reductase family 1 member B1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia (PubMed:1936586). Reduces steroids and their derivatives and prostaglandins. Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal (PubMed:12732097, PubMed:19010934, PubMed:8343525). Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides (PubMed:17381426). Plays a role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) (PubMed:21329684)
Specific Function: Aldose reductase (nadph) activity
Gene Name: AKR1B1
Uniprot ID: P15121
Uniprot Name: Aldo-keto reductase family 1 member B1
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]

Details4. Aldo-keto reductase family 1 member B10

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:12732097, PubMed:18087047, PubMed:19013440, PubMed:19563777, PubMed:9565553). Displays strong enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal (PubMed:12732097, PubMed:18087047). Plays a critical role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) (PubMed:19013440, PubMed:19563777). Displays no reductase activity towards glucose (PubMed:12732097)
Specific Function: Alcohol dehydrogenase (nadp+) activity
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]

Details5. 3',5'-cyclic-AMP phosphodiesterase 4D

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes
Specific Function: 3',5'-cyclic-amp phosphodiesterase activity
Gene Name: PDE4D
Uniprot ID: Q08499
Uniprot Name: 3',5'-cyclic-AMP phosphodiesterase 4D
Molecular Weight: 91114.1 Da

Details6. 3',5'-cyclic-AMP phosphodiesterase 4C

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes
Specific Function: 3',5'-cyclic-amp phosphodiesterase activity
Gene Name: PDE4C
Uniprot ID: Q08493
Uniprot Name: 3',5'-cyclic-AMP phosphodiesterase 4C
Molecular Weight: 79900.795 Da

Details7. cGMP-dependent 3',5'-cyclic phosphodiesterase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: cGMP-activated cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:15938621, PubMed:29392776, PubMed:9210593). Has a higher efficiency with cGMP compared to cAMP (PubMed:15938621). Plays a role in cell growth and migration (PubMed:24705027)
Specific Function: 3',5'-cyclic-amp phosphodiesterase activity
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 August 26, 2024 19:23

Exisulind

Identification

Structure for Exisulind (DB06246)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Clinical Trial & Rare Diseases Add-on Data Package

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References

References

References