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) |
|||
Target ID: P33527|||Q9UQ99 Gene ID: 4363.0 Gene Symbol: ABCC1 Target Organism: Homo sapiens (Human) |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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. | 2014-03-25 |
|
| Functional characterization of peroxisome proliferator-activated receptor-β/δ expression in colon cancer. | 2011-11 |
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| The dietary compounds resveratrol and genistein induce activating transcription factor 3 while suppressing inhibitor of DNA binding/differentiation-1. | 2011-06 |
|
| Oxidative stress is important in the pathogenesis of liver injury induced by sulindac and lipopolysaccharide cotreatment. | 2010-06-04 |
|
| Sulindac metabolites induce proteosomal and lysosomal degradation of the epidermal growth factor receptor. | 2010-04 |
|
| Phosphatidylinositol acts through mitogen-activated protein kinase to stimulate hepatic apolipoprotein A-I secretion. | 2008-12 |
|
| Nonsteroidal anti-inflammatory drugs induced endothelial apoptosis by perturbing peroxisome proliferator-activated receptor-delta transcriptional pathway. | 2008-11 |
|
| Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. | 2008-08-29 |
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| Sulindac derivatives that activate the peroxisome proliferator-activated receptor gamma but lack cyclooxygenase inhibition. | 2008-08-28 |
|
| Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs. | 2008-07-23 |
|
| Cyclooxygenase inhibitors block uterine tumorigenesis in HMGA1a transgenic mice and human xenografts. | 2008-07 |
|
| Independent generation of Abeta42 and Abeta38 peptide species by gamma-secretase. | 2008-06-20 |
|
| Effects of sulindac sulfide on the membrane architecture and the activity of gamma-secretase. | 2008-05 |
|
| Cyclooxygenase inhibitors induce apoptosis in sinonasal cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene. | 2008-04-15 |
|
| Growth compensatory role of sulindac sulfide-induced thrombospondin-1 linked with ERK1/2 and RhoA GTPase signaling pathways. | 2008-03-12 |
|
| Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells. | 2008-03-01 |
|
| Non-steroidal anti-inflammatory drugs have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro. | 2008-03 |
|
| Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation. | 2008-01-11 |
|
| Malignant transformation of normal enterocytes following downregulation of Bak expression. | 2008 |
|
| Signal peptide peptidase and gamma-secretase share equivalent inhibitor binding pharmacology. | 2007-12-21 |
|
| Up-regulation of early growth response gene 1 (EGR-1) via ERK1/2 signals attenuates sulindac sulfide-mediated cytotoxicity in the human intestinal epithelial cells. | 2007-09-01 |
|
| Insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors is common among aggressive presenilin-1 mutations. | 2007-08-24 |
|
| Desmethyl derivatives of indomethacin and sulindac as probes for cyclooxygenase-dependent biology. | 2007-07-20 |
|
| Survivin is a downstream target and effector of sulindac-sensitive oncogenic Stat3 signalling in head and neck cancer. | 2007-07 |
|
| Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives. | 2007-06 |
|
| Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon. | 2007-04-01 |
|
| Effect of genetic variants of the human flavin-containing monooxygenase 3 on N- and S-oxygenation activities. | 2007-03 |
|
| Arachidonic acid-induced gene expression in colon cancer cells. | 2006-10 |
|
| Antiangiogenic effect of sulindac sulfide could be secondary to induction of apoptosis and cell cycle arrest. | 2006-08-05 |
|
| Sulindac sulfide and exisulind inhibit expression of the estrogen and progesterone receptors in human breast cancer cells. | 2006-06-01 |
|
| Id-1 gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer. | 2006-03-15 |
|
| Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line. | 2005-12-08 |
|
| Transcriptional regulation of activating transcription factor 3 involves the early growth response-1 gene. | 2005-11 |
|
| Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1 via the early growth response gene Egr-1. | 2005-10 |
|
| Activation of protein kinase G up-regulates expression of 15-lipoxygenase-1 in human colon cancer cells. | 2005-09-15 |
|
| The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3). | 2005-05 |
|
| The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15. | 2005-03 |
|
| Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. | 2005-03 |
|
| Mechanisms of sulindac-induced apoptosis and cell cycle arrest. | 2005-02-28 |
|
| Cyclooxygenase inhibitors induce the expression of the tumor suppressor gene EGR-1, which results in the up-regulation of NAG-1, an antitumorigenic protein. | 2005-02 |
|
| The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells. | 2005-01-15 |
|
| Cyclooxygenase inhibitors induce apoptosis in oral cavity cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene. | 2004-12-24 |
|
| Selective nonsteroidal anti-inflammatory drugs induce thymosin beta-4 and alter actin cytoskeletal organization in human colorectal cancer cells. | 2004-12 |
|
| Inhibition of extracellular-signal regulated kinases 1/2 is required for apoptosis of human colon cancer cells in vitro by sulindac metabolites. | 2004-11-15 |
|
| 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. | 2004-10 |
|
| Purification and characterization of the human gamma-secretase complex. | 2004-08-03 |
|
| Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. | 2004-08 |
|
| Effect of nonsteroidal anti-inflammatory drugs on beta-catenin protein levels and catenin-related transcription in human colorectal cancer cells. | 2004-07-05 |
|
| Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines. | 2004-01-12 |
|
| 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. | 1997-06-15 |
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
| Substance Class |
Chemical
Created
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admin
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Edited
Mon Mar 31 19:17:43 GMT 2025
by
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on
Mon Mar 31 19:17:43 GMT 2025
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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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256-403-9
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TARGET -> INHIBITOR |
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PRODRUG -> METABOLITE ACTIVE |
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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ACTIVE MOIETY |
