|Systematic (IUPAC) name|
|Legal status||POM (UK) Not available in U.S.|
|PDB ligand ID||D16 (, )|
|Mol. mass||458.489 g/mol|
|(what is this?)|
Mechanism of action
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.
Structure and phase I clinical trial of the precursor drug, CB3717, was described in 1986.
- 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.
- 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.