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
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
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
Title | Date | PubMed |
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P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cells. | 2004 Sep 1 |
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BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors. | 2005 Dec 15 |
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Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: part I. | 2007 Sep |
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Dynamics of antifolate transport via the reduced folate carrier and the membrane folate receptor in murine leukaemia cells in vitro and in vivo. | 2008 Nov |
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Antifolate inhibitors of thymidylate synthase as anticancer drugs. | 2010 Nov |
Patents
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C2021
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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
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L9P2881C3H
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100000141989
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DB06163
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8279
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C1629
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CHEMBL126648
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153537-73-6
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DTXSID10165351
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696259
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135430970
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SUB107725
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ACTIVE MOIETY