Raltitrexed (Synonyms: ICI-D 1694, ZD 1694) |
| Catalog No.GC17750 |
Thymidylate synthase inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 112887-68-0
Sample solution is provided at 25 µL, 10mM.
Raltitrexed is an inhibitor of thymidylate synthase (Ki = 62 nM).[1] It inhibits the growth of L1210 mouse lymphocytic leukemia cells in vitro (IC50 = 8 nM) as well as reduces thymidylate synthase activity and completely eliminates tumors in a mouse L1210:ICR ascitic tumor model when administered at a dose of 4 mg/kg, effects that can be reversed by administration of thymidine. It also reduces tumor growth and the number of metastases in an HCT116-luc mouse xenograft model.[2] Formulations containing raltitrexed have been used in the treatment of advanced colorectal cancers.
Reference:
[1]. Jackman, A.L., Taylor, G.A., Gibson, W., et al. ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: A new agent for clinical study. Cancer Res. 51(20), 5579-5586 (1991).
[2]. Qiu, C., Li, Y., Liang, X., et al. A study of peritoneal metastatic xenograft model of colorectal cancer in the treatment of hyperthermic intraperitoneal chemotherapy with Raltitrexed. Biomed Pharmacother. 92, 149-156 (2017).
| Cell experiment [1]: | |
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Cell lines |
2 wild-type (wt) p53 (Lovo and LS174T) and 4 mutant (mt) p53 (WiDr, WiDr/F, HT29 and SW948) colon carcinoma cell lines |
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Preparation method |
The solubility of this compound in DMSO is > 154mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
50 and 100 nM; 24 and 48 hrs |
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Applications |
Raltitrexed up-regulated p53 and p21 expression in wt p53 cells, but not in mt p53 cells. In the mt p53 cells HT29 and WiDr/F, the highest induction of thymidylate synthase (6 ~ 10 folds) was observed after Raltitrexed treatment. Moreover, Raltitrexed increased Bax expression up to 5 folds in wt p53 cells, but with only a very slight induction of Bax expression in mt p53 cells. In wt p53 cells, Raltitrexed treatment hardly changed Bcl-2 expression. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6J-ApcMin/+ mice |
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Dosage form |
3 or 5 mg/kg; twice a week or five times a week |
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Applications |
In C57BL/6J-ApcMin/+ mice, Raltitrexed (3 mg/kg; twice a week) increased the average tumor number in the small intestine by 4 folds. When the dose of Raltitrexed was elevated to 5 mg/kg, five times a week, it resulted in a 10-fold increase in the average tumor number. Under all administration schedules, Raltitrexed was well-tolerated with only few treatment-related deaths occurring. Raltitrexed-induced tumors commonly occurred in the duodenum and jejunum, with few in the ileum and none in the colon. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Peters GJ, van Triest B, Backus HH, Kuiper CM, van der Wilt CL, Pinedo HM. Molecular downstream events and induction of thymidylate synthase in mutant and wild-type p53 colon cancer cell lines after treatment with 5-fluorouracil and the thymidylate synthase inhibitor raltitrexed. Eur J Cancer. 2000 May;36(7):916-24. [2]. Murphy JT, Tucker JM, Davis C, Berger FG. Raltitrexed increases tumorigenesis as a single agent yet exhibits anti-tumor synergy with 5-fluorouracil in ApcMin/+ mice. Cancer Biol Ther. 2004 Nov;3(11):1169-76. | |
| Cas No. | 112887-68-0 | SDF | |
| Synonyms | ICI-D 1694, ZD 1694 | ||
| Chemical Name | (2S)-2-[[5-[methyl-[(2-methyl-4-oxo-1H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]pentanedioic acid | ||
| Canonical SMILES | CC1=NC(=O)C2=C(N1)C=CC(=C2)CN(C)C3=CC=C(S3)C(=O)NC(CCC(=O)O)C(=O)O | ||
| Formula | C21H22N4O6S | M.Wt | 458.49 |
| Solubility | ≥ 154mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)
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