product name Raltitrexed
Description: Raltitrexed (also called Tomudex, TDX, ZD 1694) is an antimetabolite drug used in cancer chemotherapy. Raltitrexed is a thymidylate synthase inhibitor with an IC50 of 9 nM for the inhibition of L1210 cell growth. Raltitrexed induces a concentration-dependent amount of double-stranded DNA breaks. Raltitrexed increases the level of Bax protein up to a factor 5 in the Lovo and LS174T cell lines containing wt p53.
References: Eur J Cancer. 2000 May;36(7):916-24; Ann Oncol. 2002 Apr;13(4):513-22.
458.49
Formula
C21H22N4O6S
CAS No.
112887-68-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 92 mg/mL (200.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
ZD-1694
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19413575
| In Vitro |
In vitro activity: Raltitrexed induces a concentration-dependent amount of double-stranded DNA breaks. Raltitrexed increases the level of Bax protein up to a factor 5 in the Lovo and LS174T cell lines containing wt p53. Raltitrexed leads to an increase of intracellular phosphoribosyl pyrophosphate (PRPD) in the case of the HCT-8 cell line, which suggests that the cytotoxic effects of raltitrexed combined with 5-FU may be due to the increased formation of 5-FU nucleotides. Raltitrexed combined with SN-38 results in synergistic cytotoxicity at broad dose-effect ranges in human colon cancer cells. Raltitrexed is actively taken up into cells and then undergoes rapid, extensive metabolism to a series of polyglutamates, which results in potent thymidylate synthase inhibition. Raltitrexed is delivered to the brain very quickly, and could be detected at 5 min in all brain tissues. Raltitrexed combined folinic acid (5FU-FA) shows a clear schedule-dependent synergistic antiproliferative interaction as demonstrated by calculating combination indexes. Raltitrexed combined with Vorinostat produces synergistic effect paralleled by evident cell cycle perturbations with major S-phase arrest. Raltitrexed is a specific, folate-based inhibitor of thymidylate synthase with activity in advanced colorectal cancer comparable with that of fluorouracil (5-fluorouracil) plus folinic acid. Raltitrexed‘s activity is enhanced by rapid cellular entry and polyglutamation, with the polyglutamated derivatives having approximately 100-fold greater inhibitory potency than the parent compound. Kinase Assay: Cell Assay: Raltitrexed (ZD1694) is a novel quinazoline folate analog that selectively inhibits thymidylate synthase. Intracellularly, raltitrexed is polyglutamated to its active form which can be retained in cells for prolonged periods. The clearance of raltitrexed ranged from 110 to 165 ml/min per m(2), and the steady-state volume of distribution exceeded 200 l/m(2). The CSF penetration of raltitrexed was limited (0.6 to 2.0%) and drug could only be detected in the CSF following a 10 mg/m(2 )dose. ZD1694 has a spectrum of activity that only partially overlaps with 5-fluorouracil (modulated with leucovorin) against colon tumours in vitro. ZD1694 has antitumour activity in mice. ZD1694 entered clinical study and has completed Phase I and II evaluation, with activity observed in several tumour types. Appreciable activity in the Phase II colorectal study (29% objective response rate on interim analysis) led to the current Phase III study, randomised against 5-fluorouracil/leucovorin. |
|---|---|
| In Vivo | Raltitrexed could be directly transported into the brain via the olfactory pathway in rats. |
| Animal model | |
| Formulation & Dosage | |
| References | Eur J Cancer. 2000 May;36(7):916-24; Ann Oncol. 2002 Apr;13(4):513-22. |
