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 |
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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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Two opposing effects of non-steroidal anti-inflammatory drugs on the expression of the inducible cyclooxygenase. Mediation through different signaling pathways. | 2000 Sep 8 |
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Constitutive activation of NF-kappaB in Ki-ras-transformed prostate epithelial cells. | 2002 Jul 4 |
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Mesalazine causes a mitotic arrest and induces caspase-dependent apoptosis in colon carcinoma cells. | 2003 Mar |
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Exisulind and related compounds inhibit expression and function of the androgen receptor in human prostate cancer cells. | 2003 Oct 15 |
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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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Purification and characterization of the human gamma-secretase complex. | 2004 Aug 3 |
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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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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 |
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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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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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Survivin is a downstream target and effector of sulindac-sensitive oncogenic Stat3 signalling in head and neck cancer. | 2007 Jul |
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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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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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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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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 metabolites induce proteosomal and lysosomal degradation of the epidermal growth factor receptor. | 2010 Apr |
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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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Functional characterization of peroxisome proliferator-activated receptor-β/δ expression in colon cancer. | 2011 Nov |
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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
Thu Jul 06 01:50:30 UTC 2023
by
admin
on
Thu Jul 06 01:50:30 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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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 |