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
CHEBI:64212
CAS Number
59973-80-7
UNII
K619IIG2R9
DrugBank ID
DB06246
TTD ID
D0M9VE
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]
Adenosine 5'-monophosphoramidase HINT1 (HINT1) OTQIR8LF HINT1_HUMAN Gene/Protein Processing [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [6]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Gene/Protein Processing [7]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Gene/Protein Processing [8]
cGMP-dependent 3',5'-cyclic phosphodiesterase (PDE2A) OTZESF4H PDE2A_HUMAN Gene/Protein Processing [8]
cGMP-dependent protein kinase 1 (PRKG1) OTPAS4LF KGP1_HUMAN Gene/Protein Processing [9]
cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A) OTT8Q1AP PDE5A_HUMAN Gene/Protein Processing [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [5]
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 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.
6 Cyclic GMP mediates apoptosis induced by sulindac derivatives via activation of c-Jun NH2-terminal kinase 1. Clin Cancer Res. 2000 Oct;6(10):4136-41.
7 Sulindac sulfide-induced apoptosis involves death receptor 5 and the caspase 8-dependent pathway in human colon and prostate cancer cells. Cancer Res. 2001 Sep 15;61(18):6918-24.
8 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.
9 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.