Raltitrexed
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MedKoo CAT#: 100762

CAS#: 112887-68-0

Description: Raltitrexed, also known as ZD 1694, is an antimetabolite drug used in treatment of colorectal cancer since 1998. It may also be used in the treatment of malignant mesothelioma. It is an inhibitor of thymidylate synthase, and is manufactured by AstraZeneca. 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.

Chemical Structure

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Raltitrexed
CAS# 112887-68-0
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 100762
Name: Raltitrexed
CAS#: 112887-68-0
Chemical Formula: C21H22N4O6S
Exact Mass: 458.13
Molecular Weight: 458.490
Elemental Analysis: C, 55.01; H, 4.84; N, 12.22; O, 20.94; S, 6.99

Price and Availability

Size Price Availability Quantity
50g USD -1
10mg USD 50
25mg USD 90
50mg USD 150
100mg USD 250
200mg USD 450
500mg USD 950
1g USD 1450
2g USD 2150
5g USD 3750
10g USD 4950
20g USD 8950
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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

Appearance: Solid powder

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).      

Product Data:
Product Data
Instruction:
View handling instruction
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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 91.0 198.47

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.

Recalculate based on batch purity %
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.

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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.