U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C14H9ClN2O3S
Molecular Weight 320.751
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TENIDAP

SMILES

NC(=O)N1C(=O)\C(=C(/O)C2=CC=CS2)C3=C1C=CC(Cl)=C3

InChI

InChIKey=LXIKEPCNDFVJKC-QXMHVHEDSA-N
InChI=1S/C14H9ClN2O3S/c15-7-3-4-9-8(6-7)11(13(19)17(9)14(16)20)12(18)10-2-1-5-21-10/h1-6,18H,(H2,16,20)/b12-11-

HIDE SMILES / InChI

Description
Curator's Comment: the description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8909974 | https://www.ncbi.nlm.nih.gov/pubmed/7637484 | https://goo.gl/hUnLmc | https://www.ncbi.nlm.nih.gov/pubmed/23410172 | https://www.ncbi.nlm.nih.gov/pubmed/12623291 | https://www.ncbi.nlm.nih.gov/pubmed/7674236

Tenidap ([Z]-5-chloro-2,3-dihydro-3-[hydroxy-2-thienylmethylene]-2-oxo-1H-indole-1-carboxamide) is an oxindole derivative, a COX/5-LOX inhibitor and cytokine-modulating anti-inflammatory drug candidate that was under development by Pfizer as a promising potential treatment for rheumatoid arthritis. Tenidap shows potent inhibition of cyclooxygenase in vitro, that is of several magnitudes greater than 5-lipoxygenase inhibition. Lipoxygenase inhibition, however, has been difficult to document in vivo because Tenidap is highly protein bound and free drug concentrations are below those necessary for 5-lipoxygenase inhibition. However, several in-vitro activities distinguish Tenidap from conventional cyclooxygenase inhibitors. As shown with stimulated human neutrophils, tenidap inhibits activation of collagenase, lysosomal enzyme secretion, and superoxide generation, as well as aggregation and adhesion to endothelium. Furthermore, unlike Non-steroidal anti-inflammatory drugs (NSAIDs), it lowers circulating C-reactive protein (CRP) concentrations by a magnitude equivalent to hydroxychloroquine and auranofin. This result suggests an effect on the synthesis and/or release of the cytokines known to induce the acute-phase protein response-namely, IL-1, IL-6, and TNF-alpha. Tenidap, like existing second-line drugs, lowers serum IL-6 concentrations, a property not shared by NSAIDs The cytokine inhibitory effect also includes reduced in-vitro concentrations of TNF-alpha and IL-1 from both RA synovium and peripheral blood mononuclear cells. There is no immunosuppressive effect of Tenidap in either animal or clinical studies. In clinical studies. The comparisons between tenidap and other second-line agents show that Tenidap produced a faster reduction in CRP than Auranofin. The rate of withdrawal because of inefficacy was similar (18-20%) in Auranofin and Tenidap groups. The quality of life using the arthritis impact measurement scales has also been assessed Scores were better with tenidap than with NSAID monotherapy, but equivalent to the second line plus NSAID combinations. Tenidap is registered in the United States, Netherlands, and Italy but is not marketed because marketing approval was rejected by the FDA in 1996 due to liver and kidney toxicity, which was attributed to metabolites of the drug with a thiophene moiety that caused oxidative damage.

Originator

Curator's Comment: # Pfizer Inc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
52.0 nM [IC50]
2560.0 nM [IC50]
9000.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
In vitro inhibition of leukotriene B4 formation by exogeneous 5-lipoxygenase inhibitors is associated with enhanced generation of 15-hydroxy-eicosatetraenoic acid (15-HETE) by human neutrophils.
1988
Tenidap in rheumatoid arthritis. A 24-week double-blind comparison with hydroxychloroquine-plus-piroxicam, and piroxicam alone.
1995 Oct
Tenidap inhibits replication of the human immunodeficiency virus-1 in cultured cells.
1997 Jan 1
Tenidap, a novel anti-inflammatory agent, is an opener of the inwardly rectifying K+ channel hKir2.3.
2002 Jan 25
Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes.
2003 May 15
Patents

Patents

Sample Use Guides

40-120mg/day (5-year study)
Route of Administration: Oral
In Vitro Use Guide
The human astrocytoma cell line U373 MG were used for activity evaluation. Cells were grown in MEM-Earle’s medium containing 10% fetal calf scrum, glutamine, antibiotics, vitamins, amino acids and pyruvate. Cultures were grown for 5-6 days at 37 C in 5% CO2 Medium was changed one day before treatment for RNA extraction and directly prior to stimulation for IL-6 determination by ELISA. Cells were stimulated 24 h for ELISA experiments, 18 h for immunoprecipitation and 4h for RNA extraction. NSAIDs (Tenidap) were added 1 h before incubation with IL-1beta
Name Type Language
TENIDAP
INN   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
Tenidap [WHO-DD]
Common Name English
TENIDAP [MI]
Common Name English
CP-66,248
Code English
TENIDAP [USAN]
Common Name English
tenidap [INN]
Common Name English
(Z)-5-Chloro-3-(α-hydroxy-2-thenylidene)-2-oxo-1-indolinecarboxamide
Systematic Name English
CP-66248
Code English
1H-INDOLE-1-CARBOXAMIDE, 5-CHLORO-2,3-DIHYDRO-3-(HYDROXY-2-THIENYLMETHYLENE)-2-OXO-, (Z)-
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C257
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
WHO-ATC M01AX23
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
WHO-VATC QM01AX23
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL1908355
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY
FDA UNII
9K7CJ74ONH
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY
MESH
C062866
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY
DRUG CENTRAL
4728
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PRIMARY
CAS
100599-27-7
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
ALTERNATIVE
DRUG BANK
DB13481
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PRIMARY
EVMPD
SUB15484MIG
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY
CHEBI
35847
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PRIMARY
INN
6421
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EPA CompTox
DTXSID9046104
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PRIMARY
SMS_ID
100000077557
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PRIMARY
USAN
Z-70
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY
PUBCHEM
54683953
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY
CAS
120210-48-2
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY
NCI_THESAURUS
C152558
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY
MERCK INDEX
m10557
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
TENIDAP
Created by admin on Sat Dec 16 17:22:36 GMT 2023 , Edited by admin on Sat Dec 16 17:22:36 GMT 2023
PRIMARY