Details
Stereochemistry | ACHIRAL |
Molecular Formula | C20H17FO2S |
Molecular Weight | 340.411 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CSC1=CC=C(\C=C2\C(C)=C(CC(O)=O)C3=C2C=CC(F)=C3)C=C1
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-
Molecular Formula | C20H17FO2S |
Molecular Weight | 340.411 |
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P01112 Gene ID: 3265.0 Gene Symbol: HRAS Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9778042 |
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Target ID: P33527|||Q9UQ99 Gene ID: 4363.0 Gene Symbol: ABCC1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28276667 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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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 |
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PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. | 1999 Oct 29 |
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Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells. | 2000 Jun |
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Chemoprevention of intestinal polyposis in the Apcdelta716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor. | 2001 Feb 15 |
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A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. | 2001 Nov 8 |
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Diallyl disulfide (DADS) induces the antitumorigenic NSAID-activated gene (NAG-1) by a p53-dependent mechanism in human colorectal HCT 116 cells. | 2002 Apr |
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New indene-derivatives with anti-proliferative properties. | 2002 Feb 25 |
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Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53. | 2002 Mar |
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Requirement of BAX for TRAIL/Apo2L-induced apoptosis of colorectal cancers: synergism with sulindac-mediated inhibition of Bcl-x(L). | 2002 Mar 15 |
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Apo2L/TRAIL differentially modulates the apoptotic effects of sulindac and a COX-2 selective non-steroidal anti-inflammatory agent in Bax-deficient cells. | 2002 Sep 5 |
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Abeta42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) and ErbB-4 receptor and signaling through the APP intracellular domain. | 2003 Aug 15 |
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Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity. | 2003 Aug 22 |
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Gene modulation by the cyclooxygenase inhibitor, sulindac sulfide, in human colorectal carcinoma cells: possible link to apoptosis. | 2003 Jul 11 |
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Mesalazine causes a mitotic arrest and induces caspase-dependent apoptosis in colon carcinoma cells. | 2003 Mar |
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Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation. | 2003 May 16 |
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Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. | 2004 Aug |
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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 |
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Effect of nonsteroidal anti-inflammatory drugs on beta-catenin protein levels and catenin-related transcription in human colorectal cancer cells. | 2004 Jul 5 |
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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 |
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Non-steroidal anti-inflammatory drug activated gene (NAG-1) expression is closely related to death receptor-4 and -5 induction, which may explain sulindac sulfide induced gastric cancer cell apoptosis. | 2004 Oct |
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Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line. | 2005 Dec 8 |
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The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells. | 2005 Jan 15 |
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The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15. | 2005 Mar |
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Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. | 2005 Mar |
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The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3). | 2005 May |
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Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1 via the early growth response gene Egr-1. | 2005 Oct |
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Antiangiogenic effect of sulindac sulfide could be secondary to induction of apoptosis and cell cycle arrest. | 2006 Jul-Aug |
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Sulindac sulfide and exisulind inhibit expression of the estrogen and progesterone receptors in human breast cancer cells. | 2006 Jun 1 |
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Arachidonic acid-induced gene expression in colon cancer cells. | 2006 Oct |
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Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon. | 2007 Apr 1 |
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Survivin is a downstream target and effector of sulindac-sensitive oncogenic Stat3 signalling in head and neck cancer. | 2007 Jul |
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Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives. | 2007 Jun |
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Effect of genetic variants of the human flavin-containing monooxygenase 3 on N- and S-oxygenation activities. | 2007 Mar |
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Malignant transformation of normal enterocytes following downregulation of Bak expression. | 2008 |
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Cyclooxygenase inhibitors induce apoptosis in sinonasal cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene. | 2008 Apr 15 |
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Sulindac derivatives that activate the peroxisome proliferator-activated receptor gamma but lack cyclooxygenase inhibition. | 2008 Aug 28 |
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Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. | 2008 Aug 29 |
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Phosphatidylinositol acts through mitogen-activated protein kinase to stimulate hepatic apolipoprotein A-I secretion. | 2008 Dec |
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Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation. | 2008 Jan 11 |
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Non-steroidal anti-inflammatory drugs have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro. | 2008 Mar |
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Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells. | 2008 Mar 1 |
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Growth compensatory role of sulindac sulfide-induced thrombospondin-1 linked with ERK1/2 and RhoA GTPase signaling pathways. | 2008 Mar 12 |
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Nonsteroidal anti-inflammatory drugs induced endothelial apoptosis by perturbing peroxisome proliferator-activated receptor-delta transcriptional pathway. | 2008 Nov |
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Oxidative stress is important in the pathogenesis of liver injury induced by sulindac and lipopolysaccharide cotreatment. | 2010 Jun 4 |
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The dietary compounds resveratrol and genistein induce activating transcription factor 3 while suppressing inhibitor of DNA binding/differentiation-1. | 2011 Jun |
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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
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10933052
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10933052
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
Edited
Fri Dec 15 18:38:26 UTC 2023
by
admin
on
Fri Dec 15 18:38:26 UTC 2023
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Record UNII |
6UVA8S2DEY
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C1323
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C025462
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1642031
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DTXSID0049078
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49627-27-2
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C29854
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6UVA8S2DEY
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5352624
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256-403-9
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TARGET -> INHIBITOR |
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Related Record | Type | Details | ||
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PRODRUG -> METABOLITE ACTIVE |
Available evidence indicates that the biological activity resides with the sulfide metabolite.
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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ACTIVE MOIETY |