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Details

Stereochemistry ACHIRAL
Molecular Formula C20H17FO2S
Molecular Weight 340.413
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of SULINDAC SULFIDE

SMILES

CC/1=C(CC(=O)O)c2cc(ccc2\C1=C(\[H])/c3ccc(cc3)SC)F

InChI

InChIKey=LFWHFZJPXXOYNR-MFOYZWKCSA-N
InChI=1S/C20H17FO2S/c1-12-17(9-13-3-6-15(24-2)7-4-13)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-

HIDE SMILES / InChI

Molecular Formula C20H17FO2S
Molecular Weight 340.413
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Sulindac sulfide, an active metabolite of the nonsteroidal anti-inflammatory drug (NSAID) sulindac, directly binds to the Ras gene product p21ras in a non-covalent manner. Sulindac sulfide strongly inhibits Ras-induced malignant transformation and Ras/Raf dependent transactivation, due to its action at the most critical site in Ras signaling. Sulindac sulfide was proposed as a lead compound in the search for novel anti-cancer drugs, which directly inhibit Ras-mediated cell proliferation and malignant transformation. Experiments on rodents have revealed that sulindac sulfide effectively inhibited tumor growth in colorectal cancer cell xenografts mice. In addition, was shown, that sulindac sulfide inhibited ABCC1-mediated transport of appropriate endogenous and xenobiotic substrates. The drug was selectivity for ABCC1 as compared with ABCB1 and ABCG2. These properties allow designing novel ABCC1 inhibitors by chemically modifying sulindac sulfide to improve potency and selectivity to inhibit ABCC1-mediated efflux for preventing drug resistance and tumor recurrence or secondary tumor formation following chemotherapy.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P01112
Gene ID: 3265
Gene Symbol: HRAS
Target Organism: Homo sapiens (Human)
Target ID: P33527|||Q9UQ99
Gene ID: 4363
Gene Symbol: ABCC1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PubMed

PubMed

TitleDatePubMed
Apoptosis primarily accounts for the growth-inhibitory properties of sulindac metabolites and involves a mechanism that is independent of cyclooxygenase inhibition, cell cycle arrest, and p53 induction.
1997 Jun 15
PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.
1999 Oct 29
Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs.
1999 Sep 1
Diallyl disulfide (DADS) induces the antitumorigenic NSAID-activated gene (NAG-1) by a p53-dependent mechanism in human colorectal HCT 116 cells.
2002 Apr
PPARgamma-mediated antineoplastic effect of NSAID sulindac on human oral squamous carcinoma cells.
2002 Apr 20
Constitutive activation of NF-kappaB in Ki-ras-transformed prostate epithelial cells.
2002 Jul 4
Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53.
2002 Mar
Requirement of BAX for TRAIL/Apo2L-induced apoptosis of colorectal cancers: synergism with sulindac-mediated inhibition of Bcl-x(L).
2002 Mar 15
Cyclooxygenase-2 overexpression inhibits death receptor 5 expression and confers resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human colon cancer cells.
2002 Sep 1
Gene modulation by the cyclooxygenase inhibitor, sulindac sulfide, in human colorectal carcinoma cells: possible link to apoptosis.
2003 Jul 11
Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation.
2003 May 16
Sulindac metabolites induce caspase- and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells.
2003 Sep
Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid.
2004 Aug
Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines.
2004 Jan 12
Effect of nonsteroidal anti-inflammatory drugs on beta-catenin protein levels and catenin-related transcription in human colorectal cancer cells.
2004 Jul 5
Inhibition of extracellular-signal regulated kinases 1/2 is required for apoptosis of human colon cancer cells in vitro by sulindac metabolites.
2004 Nov 15
Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2.
2005 Mar
Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1 via the early growth response gene Egr-1.
2005 Oct
Sulindac sulfide and exisulind inhibit expression of the estrogen and progesterone receptors in human breast cancer cells.
2006 Jun 1
Signal peptide peptidase and gamma-secretase share equivalent inhibitor binding pharmacology.
2007 Dec 21
Survivin is a downstream target and effector of sulindac-sensitive oncogenic Stat3 signalling in head and neck cancer.
2007 Jul
Malignant transformation of normal enterocytes following downregulation of Bak expression.
2008
Cyclooxygenase inhibitors induce apoptosis in sinonasal cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene.
2008 Apr 15
Sulindac derivatives that activate the peroxisome proliferator-activated receptor gamma but lack cyclooxygenase inhibition.
2008 Aug 28
Cyclooxygenase inhibitors block uterine tumorigenesis in HMGA1a transgenic mice and human xenografts.
2008 Jul
Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.
2008 Jul 23
Independent generation of Abeta42 and Abeta38 peptide species by gamma-secretase.
2008 Jun 20
Growth compensatory role of sulindac sulfide-induced thrombospondin-1 linked with ERK1/2 and RhoA GTPase signaling pathways.
2008 Mar 12
Effects of sulindac sulfide on the membrane architecture and the activity of gamma-secretase.
2008 May
The dietary compounds resveratrol and genistein induce activating transcription factor 3 while suppressing inhibitor of DNA binding/differentiation-1.
2011 Jun
Functional characterization of peroxisome proliferator-activated receptor-β/δ expression in colon cancer.
2011 Nov
Silibinin induces apoptosis of HT29 colon carcinoma cells through early growth response-1 (EGR-1)-mediated non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) up-regulation.
2014 Mar 25
Patents

Sample Use Guides

Colorectal Cancer Cell Xenografts mice: sulindac sulfide was used at a dose of 10 mg/kg every other day to treat HCA-7 xenografts that had been implanted 7 weeks earlier. In this experiment, a significant reduction in tumor growth was observed within 2 weeks of treatment initiation.
Route of Administration: Intraperitoneal
Sulindac sulfide and inhibited colorectal cancer cell line, HCA-7 HCA-7 and HCT-116 cell growth in vitro. Both HCA-7 and HCT-116 cells showed equivalent reductions in colony number with sulfide treatment (< 50 µmol/L).
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:02:23 UTC 2021
Edited
by admin
on Sat Jun 26 09:02:23 UTC 2021
Record UNII
6UVA8S2DEY
Record Status Validated (UNII)
Record Version
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Name Type Language
SULINDAC SULFIDE
Common Name English
Z-SULINDAC SULFIDE
Common Name English
SULINDAC SULFIDE, (Z)-
Common Name English
1H-INDENE-3-ACETIC ACID, 5-FLUORO-2-METHYL-1-((4-(METHYLTHIO)PHENYL)METHYLENE)-, (1Z)-
Common Name English
CIS-SULINDAC SULFIDE
Common Name English
SULINDAC RELATED COMPOUND C
USP-RS  
Common Name English
SULINDAC SULPHIDE, (Z)-
Common Name English
SULINDAC RELATED COMPOUND C [USP]
Common Name English
SULINDAC SPECIFIED IMPURITY C [EP]
Common Name English
SULINDAC RELATED COMPOUND C [USP-RS]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1323
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
Code System Code Type Description
MESH
C025462
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
PRIMARY
EPA CompTox
49627-27-2
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
PRIMARY
CAS
49627-27-2
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
PRIMARY
NCI_THESAURUS
C29854
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
PRIMARY NCIT
FDA UNII
6UVA8S2DEY
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
PRIMARY
USP_CATALOG
1642031
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
PRIMARY USP-RS
PUBCHEM
5352624
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
PRIMARY
ECHA (EC/EINECS)
256-403-9
Created by admin on Sat Jun 26 09:02:23 UTC 2021 , Edited by admin on Sat Jun 26 09:02:23 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
Available evidence indicates that the biological activity resides with the sulfide metabolite.
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY