Details of the Drug

General Information of Drug (ID: DMBY56U)

Drug Name
EXISULIND
Synonyms Aposulind; Aptosyn; Sulindac sulfone; FGN-1; Prevatac (former Brand Name); Exisulind; (Z)-5-Fluoro-2-methyl-1-[4-(methylsulfonyl)benzylidene]-1H-indene-3-acetic acid
Indication
Disease Entry ICD 11 Status REF
Colorectal cancer 2B91.Z Phase 3 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 372.4
Logarithm of the Partition Coefficient (xlogp) 3.5
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C20H17FO4S
IUPAC Name
2-[(3Z)-6-fluoro-2-methyl-3-[(4-methylsulfonylphenyl)methylidene]inden-1-yl]acetic acid
Canonical SMILES
CC\\1=C(C2=C(/C1=C\\C3=CC=C(C=C3)S(=O)(=O)C)C=CC(=C2)F)CC(=O)O
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-
InChIKey
MVGSNCBCUWPVDA-MFOYZWKCSA-N
Cross-matching ID
PubChem CID
5472495
ChEBI ID
CHEMBL64212
CAS Number
59973-80-7
UNII
K619IIG2R9
DrugBank ID
DB06246
TTD ID
D0M9VE
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
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Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Phosphodiesterase 5A (PDE5A) TTJ0IQB PDE5A_HUMAN Modulator [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
14-3-3 protein epsilon OT3WQXNA 1433E_HUMAN Gene/Protein Processing [3]
15-hydroxyprostaglandin dehydrogenase (HPGD) OTYZI6JB PGDH_HUMAN Gene/Protein Processing [4]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Gene/Protein Processing [5]
cGMP-dependent 3',5'-cyclic phosphodiesterase (PDE2A) OTZESF4H PDE2A_HUMAN Gene/Protein Processing [5]
cGMP-dependent protein kinase 1 (PRKG1) OTPAS4LF KGP1_HUMAN Gene/Protein Processing [6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [7]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Gene/Protein Processing [7]
Cytochrome P450 4A11 (CYP4A11) OTPU5J0S CP4AB_HUMAN Gene/Protein Processing [8]
Diamine acetyltransferase 1 (SAT1) OT52AU22 SAT1_HUMAN Gene/Protein Processing [9]
Matrilysin (MMP7) OTVT3SEJ MMP7_HUMAN Gene/Protein Processing [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Colorectal cancer
ICD Disease Classification 2B91.Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Phosphodiesterase 5A (PDE5A) DTT PDE5A 1.60E-01 -0.25 -0.99
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT00085826) A Phase III Study of the Efficacy of Taxotere/Aptosyn Versus Taxotere/Placebo in Non-Small Cell Lung Cancer Patients. U.S. National Institutes of Health.
2 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.
3 Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon. Cancer Res. 2007 Apr 1;67(7):3185-91. doi: 10.1158/0008-5472.CAN-06-3431.
4 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is up-regulated by flurbiprofen and other non-steroidal anti-inflammatory drugs in human colon cancer HT29 cells. Arch Biochem Biophys. 2009 Jul 15;487(2):139-45. doi: 10.1016/j.abb.2009.05.017. Epub 2009 Jun 6.
5 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.
6 Cyclic GMP-dependent protein kinase activation and induction by exisulind and CP461 in colon tumor cells. J Pharmacol Exp Ther. 2001 Nov;299(2):583-92.
7 Activation of protein kinase G Increases the expression of p21CIP1, p27KIP1, and histidine triad protein 1 through Sp1. Cancer Res. 2008 Jul 1;68(13):5355-62.
8 Effects of acidic non-steroidal anti-inflammatory drugs on human cytochrome P450 4A11 activity: Roles of carboxylic acid and a sulfur atom in potent inhibition by sulindac sulfide. Chem Biol Interact. 2023 Sep 1;382:110644. doi: 10.1016/j.cbi.2023.110644. Epub 2023 Jul 25.
9 Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer. J Biol Chem. 2003 Nov 28;278(48):47762-75.
10 Nobiletin, a citrus flavonoid, down-regulates matrix metalloproteinase-7 (matrilysin) expression in HT-29 human colorectal cancer cells. Biosci Biotechnol Biochem. 2005 Feb;69(2):307-14. doi: 10.1271/bbb.69.307.