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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H22N4O6S
Molecular Weight 458.488
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RALTITREXED

SMILES

CN(CC1=CC2=C(C=C1)N=C(C)NC2=O)C3=CC=C(S3)C(=O)N[C@@H](CCC(O)=O)C(O)=O

InChI

InChIKey=IVTVGDXNLFLDRM-HNNXBMFYSA-N
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

HIDE SMILES / InChI

Description

Raltitrexed belongs to a group of medicines known as antimetabolites. It is used to treat cancer of the colon and rectum. It may also be used to treat other kinds of cancer, as determined by your doctor. Raltitrexed blocks an enzyme needed by the cell to live. This interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by raltitrexed, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. Raltitrexed inhibits thymidylate synthase (TS) leading to DNA fragmentation and cell death. It is transported into cells via a reduced folate carrier. Inside the cell Raltitrexed is extensively polyglutamated, which enhances thymidylate synthase inhibitory power and duration. Inhibition of this enzyme results in decreased synthesis of thymidine triphosphate which is required for DNA synthesis. Raltitrexed is used for the treatment of malignant neoplasm of colon and rectum. Although raltitrexed is not approved by the US FDA, the drug was licensed in Canada and some European countries.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
530.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Tomudex

Cmax

ValueDoseCo-administeredAnalytePopulation
567.1 ng/mL
3 mg/m² 1 times / day other, intravenous
RALTITREXED blood
Homo sapiens
736.8 ng/mL
3 mg/m² single, intravenous
RALTITREXED plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1547.9 ng × h/mL
3 mg/m² 1 times / day other, intravenous
RALTITREXED blood
Homo sapiens
2341.7 ng × h/mL
3 mg/m² single, intravenous
RALTITREXED plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
1.82 h
3 mg/m² 1 times / day other, intravenous
RALTITREXED blood
Homo sapiens
12 min
3 mg/m² single, intravenous
RALTITREXED plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
7%
RALTITREXED plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended dose is 3 mg/m2 given intravenously, as a single short, intravenous infusion in 50 to 250 ml of either 0.9% sodium chloride solution or 5% dextrose (glucose) solution. It is recommended that the infusion is given over a 15 minute period. Other drugs should not be mixed with 'Tomudex' (raltitrexed) in the same infusion container. In the absence of toxicity, treatment may be repeated every 3 weeks. Dose escalation above 3 mg/m2 is not recommended, since higher doses have been associated with an increased incidence of life-threatening or fatal toxicity.
Route of Administration: Intravenous
In Vitro Use Guide
In WiDr colon adenocarcinoma cells the cytotoxicity of 1.0 uM Raltitrexed (4 h) varied from 0% to >99% within the reported range of human serum thymidine concentrations from 500 to <50 nM, respectively.