| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: =99.03%
Raltitrexed (formerly Thaltitrexed; ICID1694; TDX, ZD-1694; D1694; ICI-D1694; trade name: Tomudex), a quinazoline folate analog, is an approved antimetabolite anticancer drug used in cancer chemotherapy for treating colorectal cancer and malignant mesothelioma. Raltitrexed inhibits the growth of L1210 cells by acting as a thymidylate synthase inhibitor, with an IC50 of 9 nM.
| Targets |
thymidylate synthase (IC50 = 9 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
Western Blot Assay
HepG2 were seeded into six-well plates and treated with different stimulants as designated. Cells were then harvested by centrifugation and lysed using cell lysis buffer to obtain total protein. Protein concentration was determined by Bradford assay kit. Proteins (30 µg) were loaded into each lane of a 10% SDS-polyacrylamide gel and transferred onto PVDF membranes (Roche, Germany). Membranes were blocked for 1 h in 5% (w/v) nonfat milk and then incubated with primary antibody at room temperature for 1 h. After being washed three times in TBST, the membranes were incubated with a horseradish peroxidase-coupled goat anti-rabbit IgG (diluted 1:5000) for 1 h at room temperature and then washed three times. Finally, expression levels of protein were detected using an enhanced chemiluminescence system ECL (Roche). Immunoblotted bands were quantified by FluorChemFC2 imaging system (Alpha Innotech, San Leandro, CA, USA), and the protein of interest was normalized to β-actin.[1] |
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| Cell Assay |
GM00637 cells are plated at a density of 3.3×105 cells per 25 cm2 flask in order to evaluate the impact of Raltitrexed on cell viability and/or growth. After 24 hours, the medium is swapped out for one supplemented with different amounts of Raltitrexed, which are present in a wide range of concentrations, from less than 1 nM to more than 1 µM. For each dosage that is tested, three cell flasks are used. The cells are refed with medium that does not contain Raltitrexed after being exposed to it for 24 hours. Cells are collected and tallied 48 hours following drug-free medium feeding. The impact of Raltitrexed on cell viability and/or growth rate is measured by comparing the cell counts of the exposed cells to the control cells that were not exposed to Raltitrexed at different doses.
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| Animal Protocol |
The experiment uses adult C57BL/6 mice weighing 19–20 g at 7-8 weeks of age. Mice are kept at 22°C with a 12-hour light/dark cycle. They are given unlimited access to tap water and regular mouse chow. The male and female mice mate overnight, and the next morning, the vaginal plugs are checked. Gestational day 0.5 is when the vaginal plug is present in the pregnant mice. Six groups of ten pregnant mice each are created at random. On gestational day 7.5, five groups receive intraperitoneal injections of varying doses of Raltitrexed (5, 10, 11.5, 13.5, and 15 mg/kg b/w). Raltitrexed is dissolved in 0.99% NaCl. On day 7.5 of gestation, the control group receives an intraperitoneal injection of 0.9% NaCl at the same volume. Pregnant mice are slaughtered on gestational day 11.5 and the embryos are studied under a dissecting microscope.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Raltitrexed is transported into cells via a reduced folate carrier. Inside the cell it is extensively polyglutamated by the enzyme folyl polyglutamate synthetase to polyglutamate forms. Biological Half-Life 198 hours |
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| Toxicity/Toxicokinetics |
Protein Binding
>93% |
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| References |
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| Additional Infomation |
ICI D1694 is a N-acyl-amino acid.
Raltitrexed (brand name Tomudex®) is a chemotherapy drug manufactured AstraZeneca Company, is an antimetabolite used in chemotherapy. It is an inhibitor of thymidylate synthase. Raltitrexed is a quinazoline folate analogue with antineoplastic activity. After transport into cells via the reduced folate carrier, raltitrexed undergoes intracellular polyglutamation and blocks the folate-binding site of thymidylate synthase, thereby inhibiting tetrahydrofolate activity and DNA replication and repair and resulting in cytotoxicity. (NCI04) Drug Indication For the treatment of malignant neoplasm of colon and rectum Mesothelioma of the pleura Mechanism of Action Raltitrexed is an antineoplastic Agents and folic acid antagonists. 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. Pharmacodynamics 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. |
| Molecular Formula |
C21H22N4O6S
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| Molecular Weight |
458.49
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| Exact Mass |
458.126
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| Elemental Analysis |
C, 55.01; H, 4.84; N, 12.22; O, 20.94; S, 6.99
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| CAS # |
112887-68-0
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| Related CAS # |
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| PubChem CID |
135400182
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Melting Point |
176-1800C
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| Index of Refraction |
1.692
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| LogP |
-1.28
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
790
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(NC1=O)=NC2=C1C=C(CN(C)C3=CC=C(C(N[C@H](C(O)=O)CCC(O)=O)=O)S3)C=C2
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| InChi Key |
IVTVGDXNLFLDRM-HNNXBMFYSA-N
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| InChi Code |
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
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| Chemical Name |
(2S)-2-[[5-[methyl-[(2-methyl-4-oxo-3H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]pentanedioic acid
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| Synonyms |
ZD-1694; ICID1694; ZD1694; D1694; ICI-D1694; D-1694; D 1694; ICID 1694; ZD 1694; TDX; trade name: Tomudex.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.1 mg/mL (4.5 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + + 45% Saline ≥ 2.1 mg/mL (4.5 mM) in 10% DMSO + 90% (20% SBE-β-CD in saline) ≥2.1 mg/mL (4.5 mM) in 10% DMSO + 90% Corn oil |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1811 mL | 10.9054 mL | 21.8107 mL | |
| 5 mM | 0.4362 mL | 2.1811 mL | 4.3621 mL | |
| 10 mM | 0.2181 mL | 1.0905 mL | 2.1811 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06118762 | Recruiting | Drug: Fruquintinib | Metastatic Colorectal Cancer | The First Affiliated Hospital of Nanchang University |
October 20, 2023 | Phase 4 |
| NCT05426811 | Not yet recruiting | Drug: Regorafenib Drug: Raltitrexed |
Regorafenib Raltitrexed |
China Medical University, China | July 1, 2022 | Phase 1 Phase 2 |
| NCT05148143 | Active Recruiting |
Drug: Raltitrexed combined with oxaplatin |
Cholangioadenoma | Second Affiliated Hospital, School of Medicine, Zhejiang University |
June 1, 2020 | Phase 2 |
| NCT05160896 | Recruiting | Drug: Raltitrexed Drug: Irinotecan |
Advanced Metastatic Colorectal Cancer |
Second Affiliated Hospital, School of Medicine, Zhejiang University |
November 12, 2021 | Phase 2 |
| NCT05231382 | Recruiting | Procedure: Oxaliplatin, fluorouracil/leucovorin (FOLFOX) treatment |
Hepatocellular Carcinoma | Sun Yat-sen University | March 28, 2022 | Phase 3 |
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