TILMACOXIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H19FN2O3S
Molecular Weight	338.397
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NC(C2CCCCC2)=C(O1)C3=CC=C(C(F)=C3)S(N)(=O)=O

InChI

InChIKey=MIMJSJSRRDZIPW-UHFFFAOYSA-N

InChI=1S/C16H19FN2O3S/c1-10-19-15(11-5-3-2-4-6-11)16(22-10)12-7-8-14(13(17)9-12)23(18,20)21/h7-9,11H,2-6H2,1H3,(H2,18,20,21)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11906292
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800009145 and http://www.genome.jp/dbget-bin/www_bget?dr:D01974

Tilmacoxib [JTE 522] is an orally active, potent and highly selective cyclo-oxygenase-2 (COX-2) inhibitor. It entered phase II clinical trials for the treatment of Familial adenomatous polyposis, rheumatoid arthritis, osteoarthritis, and acute pain in Japan, but was discontinued in 2003.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11906292	Inhibitor 8297	85.0 nM [IC50]
Hepatocellular carcinoma cells growth 1 Target ID: Hepatocellular carcinoma cells growth Sources: http://www.ncbi.nlm.nih.gov/pubmed/17914586	Inhibitor 8297
Carbonic anhydrase II 88 Target ID: CHEMBL205 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16418777	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D01974	Primary		Phase II 1132	Unknown Approved Use Unknown
Familial adenomatous polyposis 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16622748	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by JTE-522, a selective COX-2 inhibitor.	2001 Apr	11285187
Cyclooxygenase-2 stimulates production of amyloid beta-peptide in neuroblastoma x glioma hybrid NG108-15 cells.	2001 Feb 23	11181073
Cyclooxygenase-2 downregulates inducible nitric oxide synthase in rat intestinal epithelial cells.	2001 Sep	11518681
Inhibition of proliferation of gastric epithelial cells by a cyclooxygenase 2 inhibitor, JTE522, is also mediated by a PGE2-independent pathway.	2002 Apr	11966528
JTE-522-induced apoptosis in human gastric adenocarcinoma [correction of adenocarcinoma] cell line AGS cells by caspase activation accompanying cytochrome C release, membrane translocation of Bax and loss of mitochondrial membrane potential.	2002 Apr	11925595
Inhibitory effect of a selective cyclooxygenase-2 inhibitor on liver metastasis of colon cancer.	2002 Aug 10	12124799
Synergistic cytotoxicity and apoptosis of JTE-522, a selective cyclooxygenase-2 inhibitor, and 5-fluorouracil against bladder cancer.	2002 Dec	12442003
Prostacyclin synthase gene transfer modulates cyclooxygenase-2-derived prostanoid synthesis and inhibits neointimal formation in rat balloon-injured arteries.	2002 Feb 1	11834525
Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents.	2002 Jul	12114451
JTE-522, a selective COX-2 inhibitor, inhibits cell proliferation and induces apoptosis in RL95-2 cells.	2002 Jul	12100758
Changes of NF-kB, p53, Bcl-2 and caspase in apoptosis induced by JTE-522 in human gastric adenocarcinoma cell line AGS cells: role of reactive oxygen species.	2002 Jun	12046064
4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1).	2002 Mar 28	11906292
Pharmacokinetics and safety of JTE-522, a novel selective cyclooxygenase-2 inhibitor, in healthy male volunteers.	2002 Nov	12445023
Suppression of pancreatic cancer cell invasion by a cyclooxygenase-2-specific inhibitor.	2003	14669788
JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis1.	2003 Aug	12891558
Chemopreventive effect of JTE-522, a selective cyclooxygenase-2 inhibitor, on 1, 2-dimethylhydrazine-induced rat colon carcinogenesis.	2003 Dec 8	14643021
The potential for a selective cyclooxygenase-2 inhibitor in the prevention of liver metastasis in human colorectal cancer.	2003 Jan-Feb	12680220
Combination chemotherapy with JTE-522, a novel selective cyclooxygenase-2 inhibitor, and cisplatin against gastric cancer cell lines in vitro and in vivo.	2003 May-Jun	12929571
COX-2/VEGF-dependent facilitation of tumor-associated angiogenesis and tumor growth in vivo.	2003 Oct	14563940
JTE-522, a selective COX-2 inhibitor, interferes with the growth of lung metastases from colorectal cancer in rats due to inhibition of neovascularization: a vascular cast model study.	2004 Dec 20	15386343
Inhibition of azoxymethane-induced colon carcinogenesis in rats due to JTE-522, a selective cyclooxygenase-2 inhibitor.	2004 Jul-Sep	15373703
Production of prostaglandinE2 via bile acid is enhanced by trypsin and acid in normal human esophageal epithelial cells.	2004 May 21	15102519
Enhanced sensitivity of bladder cancer cells to cisplatin mediated cytotoxicity and apoptosis in vitro and in vivo by the selective cyclooxygenase-2 inhibitor JTE-522.	2004 Oct	15371874
Cyclooxygenase-2 gene induction causes CDDP resistance in colon cancer cell line, HCT-15.	2004 Sep-Oct	15517878
Selective inhibition of cyclooxygenase-2 inhibits colon cancer cell adhesion to extracellular matrix by decreased expression of beta1 integrin.	2005 Feb	15723653
Selective inhibition of cyclooxygenase (COX)-2 inhibits endothelial cell proliferation by induction of cell cycle arrest.	2005 Feb 10	15472909
JTE-522, a selective cyclooxygenase-2 inhibitor, inhibits induction but not growth and invasion of 1,2-dimethylhydrazine-induced tubular adenocarcinomas of colon in rats.	2005 Jan 20	15455344
Inhibitory effect of a selective cyclooxygenase inhibitor on the invasion-stimulating activity of orthotopic fibroblasts for scirrhous gastric cancer cells.	2005 Jul	16053517
Bilateral induction of the S-100A9 gene in response to spreading depression is modulated by the cyclooxygenase-2 activity.	2005 Jul 15	15993136
JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats.	2005 Mar 3	15743541
A synergic inhibitory-effect of combination with selective cyclooxygenase-2 inhibitor and S-1 on the peritoneal metastasis for scirrhous gastric cancer cells.	2006 Dec 8	16448745
Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial-mesenchymal interactions of growth in scirrhous gastric carcinoma.	2007 Feb 1	17096355
Mechanisms of anti-proliferative effect of JTE-522, a selective cyclooxygenase-2 inhibitor, on human liver cancer cells.	2007 Nov	17914586
Enhancement of the sensitivity of renal cell carcinoma cells to fas-mediated cytotoxicity and apoptosis by the selective cyclooxygenase-2 inhibitor JTE-522.	2010	20389170
Preventive effect of JTE-522, a selective cyclooxygenase-2 inhibitor, on DEN-induced hepatocarcinogenesis in rats.	2010 May	20434301

Patents

Sample Use Guides

In Vivo Use Guide

50 mg or 200 mg, once daily orally for 26 weeks.

Route of Administration: Oral

In Vitro Use Guide

Escalating doses (100 nM to 100 uM) of Tilmacoxib (JTE-522) significantly inhibited the growth of all HCC cells in a dose- and time-dependent manner.

Name

Type

Language

TILMACOXIB

Official Name

English

TILMACOXIB [USAN]

Common Name

English

JTE-522

Code

English

JTP-19605

Code

English

RWJ-57504

Code

English

TILMACOXIB [JAN]

Common Name

English

BENZENESULFONAMIDE, 4-(4-CYCLOHEXYL-2-METHYL-5-OXAZOLYL)-2-FLUORO-

Systematic Name

English

4-(4-Cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide

Systematic Name

English

tilmacoxib [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1323