Raltitrexed

Raltitrexed

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 Y
ATC code	L01BA03
PubChem	CID 104758
DrugBank	DB00293
ChemSpider	94568 Y
UNII	FCB9EGG971 Y
KEGG	D01064 Y
ChEMBL	CHEMBL225071 Y
Chemical data
Formula	C21H22N4O6S
Mol. mass	458.489 g/mol
SMILES O=C(c3sc(N(C)Cc2cc1C(=O)\N=C(/Nc1cc2)C)cc3)N[C@H](C(=O)O)CCC(=O)O
InChI InChI=1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)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 Y Key:IVTVGDXNLFLDRM-HNNXBMFYSA-N Y
Y (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

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

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.

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

External links

• Raltitrexed bound to proteins in the PDB