Synonym
D1694; ICID1694; ZD1694; ZD 1694; ZD-1694; TDX; brand name: Tomudex.
IUPAC/Chemical Name
(S)-2-(5-(methyl((2-methyl-4-oxo-1,4-dihydroquinazolin-6-yl)methyl)amino)thiophene-2-carboxamido)pentanedioic acid
InChi Key
IVTVGDXNLFLDRM-HNNXBMFYSA-N
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
SMILES Code
O=C(O)[C@@H](NC(C1=CC=C(N(C)CC2=CC3=C(NC(C)=NC3=O)C=C2)S1)=O)CCC(O)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
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 Thymidine synthase. Raltitrexed is fully active after polyglutamylation, which allows cellular retention of the drug. By inhibiting Thymidine 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. [source: http://en.wikipedia.org/wiki/Raltitrexed).
Biological target:
Raltitrexed is a thymidylate synthase inhibitor with an IC50 of 9 nM for the inhibition of L1210 cell growth. 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, resulting in cytotoxicity.
In vitro activity:
Raltitrexed enhanced the antitumor effects of anlotinib on human esophageal squamous cell carcinoma cells by down-regulating phosphorylation of Akt and Erk.
Reference: BMC Cancer. 2023 Mar 4;23(1):207. https://pubmed.ncbi.nlm.nih.gov/36870981/
In vivo activity:
Raltitrexed was able to prevent mortality and reduce the number of tachyzoites in the peritoneal fluid and liver imprints of mice infected with Toxoplasma gondii. Raltitrexed has important protective activities against the T. gondii RH strain.
Reference: Parasitol Res. 2018 May;117(5):1465-1471. https://pubmed.ncbi.nlm.nih.gov/29550996/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
91.0 |
198.47 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
458.49
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Zhen H, Tian J, Li G, Zhao P, Zhang Y, Che J, Cao B. Raltitrexed enhanced antitumor effect of anlotinib in human esophageal squamous carcinoma cells on proliferation, invasiveness, and apoptosis. BMC Cancer. 2023 Mar 4;23(1):207. doi: 10.1186/s12885-023-10691-y. PMID: 36870981; PMCID: PMC9985835.
2. Hu C, Chen X, Lin X, Dai J, Yu J. Raltitrexed regulates proliferation and apoptosis of HGC-27 cells by upregulating RSK4. BMC Pharmacol Toxicol. 2022 Aug 28;23(1):65. doi: 10.1186/s40360-022-00605-2. PMID: 36031631; PMCID: PMC9420250.
3. de Paula Reis M, de Lima DA, Pauli KB, Andreotti CEL, de Moraes ALS, Gonçalves DD, Navarro IT, Bueno PSA, Seixas FAV, Gasparotto Junior A, Lourenço ELB. Molecular docking to Toxoplasma gondii thymidylate synthase-dihydrofolate reductase and efficacy of raltitrexed in infected mice. Parasitol Res. 2018 May;117(5):1465-1471. doi: 10.1007/s00436-018-5835-5. Epub 2018 Mar 17. PMID: 29550996.
4. 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. doi: 10.4161/cbt.3.11.1220. Epub 2004 Nov 2. PMID: 15539941.
In vitro protocol:
1. Zhen H, Tian J, Li G, Zhao P, Zhang Y, Che J, Cao B. Raltitrexed enhanced antitumor effect of anlotinib in human esophageal squamous carcinoma cells on proliferation, invasiveness, and apoptosis. BMC Cancer. 2023 Mar 4;23(1):207. doi: 10.1186/s12885-023-10691-y. PMID: 36870981; PMCID: PMC9985835.
2. Hu C, Chen X, Lin X, Dai J, Yu J. Raltitrexed regulates proliferation and apoptosis of HGC-27 cells by upregulating RSK4. BMC Pharmacol Toxicol. 2022 Aug 28;23(1):65. doi: 10.1186/s40360-022-00605-2. PMID: 36031631; PMCID: PMC9420250.
In vivo protocol:
1. de Paula Reis M, de Lima DA, Pauli KB, Andreotti CEL, de Moraes ALS, Gonçalves DD, Navarro IT, Bueno PSA, Seixas FAV, Gasparotto Junior A, Lourenço ELB. Molecular docking to Toxoplasma gondii thymidylate synthase-dihydrofolate reductase and efficacy of raltitrexed in infected mice. Parasitol Res. 2018 May;117(5):1465-1471. doi: 10.1007/s00436-018-5835-5. Epub 2018 Mar 17. PMID: 29550996.
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. doi: 10.4161/cbt.3.11.1220. Epub 2004 Nov 2. PMID: 15539941.
1: Surmont VF, van Meerbeeck JP. Raltitrexed in mesothelioma. Expert Rev Anticancer Ther. 2011 Oct;11(10):1481-90. Review. PubMed PMID: 21999120.
2: Wilson KS, Malfair Taylor SC. Raltitrexed: optimism and reality. Expert Opin Drug Metab Toxicol. 2009 Nov;5(11):1447-54. Review. PubMed PMID: 19863453.
3: Hind D, Tappenden P, Tumur I, Eggington S, Sutcliffe P, Ryan A. The use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer: systematic review and economic evaluation. Health Technol Assess. 2008 May;12(15):iii-ix, xi-162. Review. PubMed PMID: 18462574.
4: Cao S, Bhattacharya A, Durrani FA, Fakih M. Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Expert Opin Pharmacother. 2006 Apr;7(6):687-703. Review. PubMed PMID: 16556086.
5: Van Cutsem E, Cunningham D, Maroun J, Cervantes A, Glimelius B. Raltitrexed: current clinical status and future directions. Ann Oncol. 2002 Apr;13(4):513-22. Review. PubMed PMID: 12056700.
6: Lloyd Jones M, Hummel S, Bansback N, Orr B, Seymour M. A rapid and systematic review of the evidence for the clinical effectiveness and cost-effectiveness of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Health Technol Assess. 2001;5(25):1-128. Review. PubMed PMID: 11990245.
7: Cunningham D, Zalcberg J, Maroun J, James R, Clarke S, Maughan TS, Vincent M, Schulz J, González Barón M, Facchini T. Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. a review of phase II/III trials. Eur J Cancer. 2002 Mar;38(4):478-86. Review. PubMed PMID: 11872339.
8: Caponigro F, Avallone A, Budillon A, Comella P, Comella G. Raltitrexed/5-fluorouracil-based combination chemotherapy regimens in anticancer therapy. Anticancer Drugs. 2001 Jul;12(6):489-97. Review. PubMed PMID: 11459994.
9: Clarke SJ, Beale PJ, Rivory LP. Clinical and preclinical pharmacokinetics of raltitrexed. Clin Pharmacokinet. 2000 Dec;39(6):429-43. Review. PubMed PMID: 11192475.
10: Royce ME, Hoff PM, Padzur R. Novel chemotherapy agents for colorectal cancer: oral fluoropyrimidines, oxaliplatin, and raltitrexed. Curr Oncol Rep. 1999;1(2):161-7. Review. PubMed PMID: 11122814.
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