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 |
|---|---|---|
| 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 |
|
| Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. | 2004 Aug |
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| Purification and characterization of the human gamma-secretase complex. | 2004 Aug 3 |
|
| Selective nonsteroidal anti-inflammatory drugs induce thymosin beta-4 and alter actin cytoskeletal organization in human colorectal cancer cells. | 2004 Dec |
|
| Cyclooxygenase inhibitors induce apoptosis in oral cavity cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene. | 2004 Dec 24 |
|
| 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 |
|
| 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 |
|
| Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line. | 2005 Dec 8 |
|
| 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 Feb |
|
| Mechanisms of sulindac-induced apoptosis and cell cycle arrest. | 2005 Feb 28 |
|
| The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells. | 2005 Jan 15 |
|
| 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 |
|
| Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. | 2005 Mar |
|
| The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3). | 2005 May |
|
| Transcriptional regulation of activating transcription factor 3 involves the early growth response-1 gene. | 2005 Nov |
|
| Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1 via the early growth response gene Egr-1. | 2005 Oct |
|
| Activation of protein kinase G up-regulates expression of 15-lipoxygenase-1 in human colon cancer cells. | 2005 Sep 15 |
|
| Antiangiogenic effect of sulindac sulfide could be secondary to induction of apoptosis and cell cycle arrest. | 2006 Jul-Aug |
|
| Sulindac sulfide and exisulind inhibit expression of the estrogen and progesterone receptors in human breast cancer cells. | 2006 Jun 1 |
|
| Id-1 gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer. | 2006 Mar 15 |
|
| Arachidonic acid-induced gene expression in colon cancer cells. | 2006 Oct |
|
| Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon. | 2007 Apr 1 |
|
| Insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors is common among aggressive presenilin-1 mutations. | 2007 Aug 24 |
|
| 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 |
|
| Desmethyl derivatives of indomethacin and sulindac as probes for cyclooxygenase-dependent biology. | 2007 Jul 20 |
|
| Genetic polymorphisms of human flavin-containing monooxygenase 3: implications for drug metabolism and clinical perspectives. | 2007 Jun |
|
| Effect of genetic variants of the human flavin-containing monooxygenase 3 on N- and S-oxygenation activities. | 2007 Mar |
|
| 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 Sep 1 |
|
| 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 |
|
| Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. | 2008 Aug 29 |
|
| Phosphatidylinositol acts through mitogen-activated protein kinase to stimulate hepatic apolipoprotein A-I secretion. | 2008 Dec |
|
| Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation. | 2008 Jan 11 |
|
| 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 |
|
| Non-steroidal anti-inflammatory drugs have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro. | 2008 Mar |
|
| Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells. | 2008 Mar 1 |
|
| 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 |
|
| Nonsteroidal anti-inflammatory drugs induced endothelial apoptosis by perturbing peroxisome proliferator-activated receptor-delta transcriptional pathway. | 2008 Nov |
|
| Sulindac metabolites induce proteosomal and lysosomal degradation of the epidermal growth factor receptor. | 2010 Apr |
|
| Oxidative stress is important in the pathogenesis of liver injury induced by sulindac and lipopolysaccharide cotreatment. | 2010 Jun 4 |
|
| 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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 17 00:52:01 UTC 2022
by
admin
on
Sat Dec 17 00:52:01 UTC 2022
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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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| Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
| 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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| Related Record | Type | Details | ||
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
