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-
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 |
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| Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma cells. | 2000 Jun |
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| Cyclic GMP mediates apoptosis induced by sulindac derivatives via activation of c-Jun NH2-terminal kinase 1. | 2000 Oct |
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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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| 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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| 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 metabolites induce caspase- and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells. | 2003 Sep |
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| Cyclooxygenase inhibitors induce apoptosis in oral cavity cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene. | 2004 Dec 24 |
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| Modulation of beta-amyloid metabolism by non-steroidal anti-inflammatory drugs in neuronal cell cultures. | 2004 Jan |
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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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| 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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| Mechanisms of sulindac-induced apoptosis and cell cycle arrest. | 2005 Feb 28 |
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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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| Activation of protein kinase G up-regulates expression of 15-lipoxygenase-1 in human colon cancer cells. | 2005 Sep 15 |
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| Id-1 gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer. | 2006 Mar 15 |
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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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| Desmethyl derivatives of indomethacin and sulindac as probes for cyclooxygenase-dependent biology. | 2007 Jul 20 |
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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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| 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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| 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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| The dietary compounds resveratrol and genistein induce activating transcription factor 3 while suppressing inhibitor of DNA binding/differentiation-1. | 2011 Jun |
|
| 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
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C1323
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C025462
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1642031
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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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ACTIVE MOIETY
PRODRUG (METABOLITE ACTIVE)
