Thymidylate synthase inhibitor

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Thymidylate synthase inhibitors are chemical agents which inhibit the enzyme thymidylate synthase and have potential as an anticancer chemotherapy. [1] This inhibition prevents the methylation of C5 of deoxyuridine monophosphate (dUMP) thereby inhibiting the synthesis of deoxythymidine monophosphate (dTMP). The downstream effect is promotion of cell death because cells would not be able to properly undergo DNA synthesis if they are lacking dTMP, a necessary precursor to dTTP. [2] Five agents were in clinical trials in 2002: raltitrexed, pemetrexed, nolatrexed, ZD9331, and GS7904L. [3]

Examples include

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HAT medium

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{{Drugbox | verifiedrevid = 464379925 | IUPAC_name = N-[(5-{methyl[ methyl]amino}-2-thienyl)carbonyl]-L-glutamic acid | image = Raltitrexed.svg | image2 = Raltitrexed ball-and-stick.png | tradename = | = Micromedex Detailed Consumer Information | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_UK = POM | legal_US = Not available | legal_status = | routes_of_administration = Intravenous | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | IUPHAR_ligand = 7403 | CAS_number_Ref =   | CAS_number = 112887-68-0 | ATC_prefix = L01 | ATC_suffix = BA03 | ATC_supplemental = | PubChem = 104758 | DrugBank_Ref =   | DrugBank = DB00293 | ChemSpiderID_Ref =   | ChemSpiderID = 94568 | UNII_Ref =   | UNII = FCB9EGG971 | KEGG_Ref =   | KEGG = D01064 | ChEMBL_Ref =   | ChEMBL = 225071 | PDB_ligand = D16 | C=21 | H=22 | N=4 | O=6 | S=1 | smiles = O=C(c3sc cc3)N[C@H](C O)CCC(=O)O | StdInChI_Ref =   | StdInChI = 1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13 19 23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21 31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1 | StdInChIKey_Ref =   | StdInChIKey = IVTVGDXNLFLDRM-HNNXBMFYSA-N }}

Thymidylate synthase

Thymidylate synthase (TS) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUMP arise. Both cause DNA damage.

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Thymidylate synthase (FAD)

In enzymology, a thymidylate synthase (FAD) (EC is an enzyme that catalyzes the chemical reaction

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OSI-7904 is a noncompetitive liposomal thymidylate synthase inhibitor. OSI-7904 is a benzoquinazoline folate analog with antineoplastic activity. As a thymidylate synthase inhibitor, OSI-7904 noncompetitively binds to thymidylate synthase, resulting in inhibition of thymine nucleotide synthesis and DNA replication.


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Thymidylate kinase

Thymidylate kinase catalyzes the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium:


Trifluridine/tipiracil, sold under the brand name Lonsurf, is a fixed-dose combination medication that is used as a third- or fourth-line treatment of metastatic colorectal cancer or gastric cancer, after chemotherapy and targeted therapeutics have failed. It is a combination of two active pharmaceutical ingredients: trifluridine, a nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor. Tipiracil prevents rapid metabolism of trifluridine, increasing the bioavailability of trifluridine.

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ONX-0801 is an experimental drug that has been developed to target ovarian cancer. It is a folate receptor alpha mediated thymidylate synthase inhibitor.

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Fluorodeoxyuridylate Chemical compound

Fluorodeoxyuridylate, also known as FdUMP, 5-Fluoro-2'-deoxyuridylate, or 5-Fluoro-2'-deoxyuridine 5'-monophosphate sodium salt, is a molecule formed in vivo from 5-fluorouracil or 5-fluorodeoxyuridin.


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