SULINDAC SULFIDE

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

Structure Search

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-

HIDE SMILES / InChI

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9778042 | https://www.ncbi.nlm.nih.gov/pubmed/28276667 | https://www.ncbi.nlm.nih.gov/pubmed/10933052

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
GTPase HRas 2 Target ID: P01112 Gene ID: 3265.0 Gene Symbol: HRAS Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9778042	Inhibitor 8228
Multidrug resistance-associated protein 1 15 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	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Colorectal cancer 99 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10933052	Primary		Preclinical	Unknown Approved Use Unknown

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	9192825
Two opposing effects of non-steroidal anti-inflammatory drugs on the expression of the inducible cyclooxygenase. Mediation through different signaling pathways.	2000 Sep 8	10866999
Constitutive activation of NF-kappaB in Ki-ras-transformed prostate epithelial cells.	2002 Jul 4	12085227
Mesalazine causes a mitotic arrest and induces caspase-dependent apoptosis in colon carcinoma cells.	2003 Mar	12663503
Exisulind and related compounds inhibit expression and function of the androgen receptor in human prostate cancer cells.	2003 Oct 15	14581372
Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid.	2004 Aug	15300575
Purification and characterization of the human gamma-secretase complex.	2004 Aug 3	15274632
Effect of nonsteroidal anti-inflammatory drugs on beta-catenin protein levels and catenin-related transcription in human colorectal cancer cells.	2004 Jul 5	15188006
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	15509713
The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells.	2005 Jan 15	15561105
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	15767558
Antiangiogenic effect of sulindac sulfide could be secondary to induction of apoptosis and cell cycle arrest.	2006 Jul-Aug	16886631
Sulindac sulfide and exisulind inhibit expression of the estrogen and progesterone receptors in human breast cancer cells.	2006 Jun 1	16740773
Arachidonic acid-induced gene expression in colon cancer cells.	2006 Oct	16704987
Survivin is a downstream target and effector of sulindac-sensitive oncogenic Stat3 signalling in head and neck cancer.	2007 Jul	17566705
Desmethyl derivatives of indomethacin and sulindac as probes for cyclooxygenase-dependent biology.	2007 Jul 20	17602619
Effect of genetic variants of the human flavin-containing monooxygenase 3 on N- and S-oxygenation activities.	2007 Mar	17142560
Cyclooxygenase inhibitors induce apoptosis in sinonasal cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene.	2008 Apr 15	18076062
Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation.	2008 Aug 29	18759972
Phosphatidylinositol acts through mitogen-activated protein kinase to stimulate hepatic apolipoprotein A-I secretion.	2008 Dec	19013290
Non-steroidal anti-inflammatory drugs have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro.	2008 Mar	18164319
Sulindac metabolites induce proteosomal and lysosomal degradation of the epidermal growth factor receptor.	2010 Apr	20332299
Oxidative stress is important in the pathogenesis of liver injury induced by sulindac and lipopolysaccharide cotreatment.	2010 Jun 4	20371263
The dietary compounds resveratrol and genistein induce activating transcription factor 3 while suppressing inhibitor of DNA binding/differentiation-1.	2011 Jun	21554132
Functional characterization of peroxisome proliferator-activated receptor-β/δ expression in colon cancer.	2011 Nov	21400612
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	24440808

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Thu Jul 06 01:50:30 UTC 2023` Edited by `admin` on `Thu Jul 06 01:50:30 UTC 2023`
Record UNII	6UVA8S2DEY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SULINDAC SULFIDE

Common Name

English

Z-SULINDAC SULFIDE

Common Name

English

SULINDAC SULFIDE, (Z)-

Common Name

English

1H-INDENE-3-ACETIC ACID, 5-FLUORO-2-METHYL-1-((4-(METHYLTHIO)PHENYL)METHYLENE)-, (1Z)-

Common Name

English

SULINDAC RELATED COMPOUND C [USP IMPURITY]

Common Name

English

CIS-SULINDAC SULFIDE

Common Name

English

SULINDAC RELATED COMPOUND C

Common Name

English

SULINDAC IMPURITY C [EP IMPURITY]

Common Name

English

SULINDAC SULPHIDE, (Z)-

Common Name

English

SULINDAC RELATED COMPOUND C [USP-RS]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1323