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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H25FN8O4
Molecular Weight 532.5263
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PLEVITREXED

SMILES

CC1=NC(=O)C2=C(N1)C=C(C)C(CN(CC#C)C3=CC(F)=C(C=C3)C(=O)N[C@@H](CCC4=NN=NN4)C(O)=O)=C2

InChI

InChIKey=IEJSCSAMMLUINT-NRFANRHFSA-N
InChI=1S/C26H25FN8O4/c1-4-9-35(13-16-11-19-22(10-14(16)2)28-15(3)29-25(19)37)17-5-6-18(20(27)12-17)24(36)30-21(26(38)39)7-8-23-31-33-34-32-23/h1,5-6,10-12,21H,7-9,13H2,2-3H3,(H,30,36)(H,38,39)(H,28,29,37)(H,31,32,33,34)/t21-/m0/s1

HIDE SMILES / InChI

Molecular Formula C26H25FN8O4
Molecular Weight 532.5263
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Plevitrexed is a rationally designed, orally bioavailable, nonpolyglutamatable quinazoline antifolate that is a selective inhibitor of thymidylate synthase with potent antineoplastic activity and the ability to overcome antifolate resistance due to decreased folylpolyglutamate synthetase activity. It also features a lower toxicity than polyglutamatable thymidylate synthase inhibitors, presumably due to a lesser cellular retention. Plevitrexed is primarily transported into the cells via reduced folate carrier and selectively binds to the folate-binding site of thymidylate synthase with high affinity. Plevitrexed was assessed and in preclinical studies against a panel of human ovarian cancer cell lines and in several phase II clinical studies for the treatment of various solid cancers including colorectal, gastric, pancreatic and ovarian cancer. The combination of plevitrexed and carboplatin is well tolerated with no significant pharmacokinetic interaction between the two drugs - antitumor activity in platinum-pretreated gynecological malignancy was demonstrated.

Approval Year

PubMed

PubMed

TitleDatePubMed
Design and synthesis of potent non-polyglutamatable quinazoline antifolate thymidylate synthase inhibitors.
1999 Sep 23
P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cells.
2004 Sep 1
Antifolate inhibitors of thymidylate synthase as anticancer drugs.
2010 Nov
Development and binding mode assessment of N-[4-[2-propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-D-glutamic acid (BGC 945), a novel thymidylate synthase inhibitor that targets tumor cells.
2013 Jul 11
Patents

Patents

Substance Class Chemical
Created
by admin
on Fri Dec 15 15:52:49 GMT 2023
Edited
by admin
on Fri Dec 15 15:52:49 GMT 2023
Record UNII
L9P2881C3H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PLEVITREXED
INN   MART.   WHO-DD  
INN  
Official Name English
(2S)-2-((4-(((2,7-DIMETHYL-4-OXO-1,4-DIHYDROQUINAZOLIN-6-YL)METHYL)(PROP-2-YNYL)AMINO)-2-FLUOROBENZOYL)AMINO)-4-(1H-TETRAZOL-5-YL)BUTANOIC ACID
Systematic Name English
PLEVITREXED [MART.]
Common Name English
BGC-9331
Code English
ZD-9331
Code English
NSC-696259
Code English
ZD9331
Code English
Plevitrexed [WHO-DD]
Common Name English
plevitrexed [INN]
Common Name English
1H-TETRAZOLE-5-BUTANOIC ACID, .ALPHA.-((4-(((1,4-DIHYDRO-2,7-DIMETHYL-4-OXO-6-QUINAZOLINYL)METHYL)-2-PROPYNYLAMINO)-2-FLUOROBENZOYL)AMINO)-, (.ALPHA.S)-
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2021
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
NCI_THESAURUS C511
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
Code System Code Type Description
FDA UNII
L9P2881C3H
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
SMS_ID
100000141989
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
DRUG BANK
DB06163
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
INN
8279
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
NCI_THESAURUS
C1629
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
ChEMBL
CHEMBL126648
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
CAS
153537-73-6
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
EPA CompTox
DTXSID10165351
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
NSC
696259
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
PUBCHEM
135430970
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
EVMPD
SUB107725
Created by admin on Fri Dec 15 15:52:49 GMT 2023 , Edited by admin on Fri Dec 15 15:52:49 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
ENANTIOMER -> ENANTIOMER
RACEMATE -> ENANTIOMER
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ACTIVE MOIETY