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Details

Stereochemistry ACHIRAL
Molecular Formula C35H40N2O6
Molecular Weight 584.7019
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of LINETASTINE

SMILES

CCOC(=O)OC1=CC=C(\C=C\C=C\C(=O)NCCN2CCC(CC2)OC(C3=CC=CC=C3)C4=CC=CC=C4)C=C1OC

InChI

InChIKey=LUOUCHOLMUUZBO-SVSXJNCISA-N
InChI=1S/C35H40N2O6/c1-3-41-35(39)43-31-19-18-27(26-32(31)40-2)12-10-11-17-33(38)36-22-25-37-23-20-30(21-24-37)42-34(28-13-6-4-7-14-28)29-15-8-5-9-16-29/h4-19,26,30,34H,3,20-25H2,1-2H3,(H,36,38)/b12-10+,17-11+

HIDE SMILES / InChI

Molecular Formula C35H40N2O6
Molecular Weight 584.7019
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 2
Optical Activity NONE

Linetastine has anti-inflammatory and anticarcinogenic effects. It is a potent inhibitor of 5-lipoxygenase. It also inhibits histamine release and epidermal cyclooxygenase activity. It also markedly inhibited TPA-stimulated leukotriene B4 formation, but inhibited formation of prostaglandin E2, a cyclooxygenase product, only slightly. This suggested that neither cyclooxygenase inhibition nor antihistaminic activity were essential to the anti-inflammatory action of linetastine. The anti-inflammatory effect of oral linetastine is probably due to 5-lipoxygenase inhibition. Oral administration of linetastine almost completely suppressed Cyp1a1 mRNA levels in mouse epidermis induced by a topical application of 3-methylcholanthrene or benzo[a]pyrene to mouse skin. Oral administration of linetastine inhibited DMBA-caused skin tumor initiation at least in part by inhibiting Cyp1a1 mRNA induction and epidermal aryl hydrocarbon hydroxylase activity. Linetastine had been in phase II clinical trial for the treatment of allergic rhinitis. However, this study was discontinued.

Approval Year

PubMed

PubMed

TitleDatePubMed
Inhibition of two-stage skin carcinogenesis as well as complete skin carcinogenesis by oral administration of TMK688, a potent lipoxygenase inhibitor.
1994 May
Anti-inflammatory action of orally active 5-lipoxygenase inhibitor TMK688.
1994 May
Inhibitory effect of TMK688 on skin tumor initiation caused by 7,12-dimethylbenz[a]anthracene in relation to inhibition of aryl hydrocarbon hydroxylase activity and Cyp1a1 mRNA induction.
1996 Aug
The inhibitory effect of TMK688, a novel anti-allergic drug having both 5-lipoxygenase inhibitory activity and anti-histamine activity, against bronchoconstriction, leukotriene production and inflammatory cell infiltration in sensitized guinea pigs.
1997 Jan
Mechanisms of non-drowsiness after oral administration of TMK688, a novel antiallergic drug.
1998 Oct
Nitric oxide, superoxide radicals and mast cells in pathogenesis of indomethacin-induced small intestinal lesions in rats.
1999 Mar
Inhibitory effect of TMK-688 on late asthmatic responses as well as T-cell and eosinophilic infiltration in guinea pigs with asthmatic reactions.
2000 Feb
Preview of potential therapeutic applications of leukotriene B4 inhibitors in dermatology.
2000 Sep-Oct
Pathogenic importance of cysteinyl leukotrienes in development of gastric lesions induced by ischemia/reperfusion in mice.
2010 Apr
Patents

Patents

Sample Use Guides

30 mg/kg at 6 h and 30 min prior to and at 30 min after a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA)
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:22:59 UTC 2023
Edited
by admin
on Fri Dec 15 16:22:59 UTC 2023
Record UNII
7U248Z56LA
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LINETASTINE
INN  
INN  
Official Name English
linetastine [INN]
Common Name English
(2E,4E)-N-(2-(4-(DIPHENYLMETHOXY)PIPERIDINO)ETHYL)-5-(4-HYDROXY-3-METHOXYPHENYL)-2,4-PENTADIENAMIDE ETHYL CARBONATE (ESTER)
Common Name English
LINAZOLAST [JAN]
Common Name English
LINAZOLAST
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29578
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL314338
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
NCI_THESAURUS
C66014
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
INN
7411
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
PUBCHEM
6439232
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
EVMPD
SUB08519MIG
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
FDA UNII
7U248Z56LA
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
CAS
159776-68-8
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
SMS_ID
100000082336
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
KEGG
D09850
Created by admin on Fri Dec 15 16:22:59 UTC 2023 , Edited by admin on Fri Dec 15 16:22:59 UTC 2023
PRIMARY
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TARGET -> INHIBITOR
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