Raltitrexed

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Raltitrexed
Raltitrexed.svg
Raltitrexed ball-and-stick.png
Systematic (IUPAC) name
N-[(5-{methyl[(2-methyl-4-oxo-1,4-dihydroquinazolin-6-yl)methyl]amino}-2-thienyl)carbonyl]-L-glutamic acid
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
Legal status POM (UK) Not available in U.S.
Routes Intravenous
Identifiers
CAS number 112887-68-0 YesY
ATC code L01BA03
PubChem CID 104758
DrugBank DB00293
ChemSpider 94568 YesY
UNII FCB9EGG971 YesY
KEGG D01064 YesY
ChEMBL CHEMBL225071 YesY
PDB ligand ID D16 (PDBe, RCSB PDB)
Chemical data
Formula C21H22N4O6S 
Mol. mass 458.489 g/mol
 YesY (what is this?)  (verify)

Raltitrexed (Tomudex, TDX, ZD 1694) is an antimetabolite drug used in cancer chemotherapy. It is an inhibitor of thymidylate synthase, and is manufactured by AstraZeneca.[1]

Uses[edit]

Used in treatment of colorectal cancer since 1998. It may also be used in the treatment of malignant mesothelioma.[2]

Mechanism of action[edit]

Raltitrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites, which inhibit one or more of three enzymes that use folate and deriavtives as substrates: DHFR, GARFT and thymidylate synthase. Raltitrexed is fully active after polyglutamylation, which allows cellular retention of the drug.

By inhibiting Thymidylate synthase (TS), thus formation of precursor pyrimidine nucleotides, raltitrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.

Inhibition of L1210 cell growth in culture IC50 = 9 nM, is one of the strongest antimetabolites in use.

Structure and phase I clinical trial of the precursor drug, CB3717, was described in 1986.[3]

References[edit]

  1. ^ Widemann BC, Balis FM, Godwin KS, McCully C, Adamson PC (1999). "The plasma pharmacokinetics and cerebrospinal fluid penetration of the thymidylate synthase inhibitor raltitrexed (Tomudex) in a nonhuman primate model". Cancer Chemother. Pharmacol. 44 (6): 439–43. PMID 10550563. 
  2. ^ [1]
  3. ^ Calvert AH, Alison DL, Harland SJ, et al. (August 1986). "A phase I evaluation of the quinazoline antifolate thymidylate synthase inhibitor, N10-propargyl-5,8-dideazafolic acid, CB3717". J. Clin. Oncol. 4 (8): 1245–52. PMID 3734849.