Home DNA Damage/DNA Repair Thymidylate Synthase inhibitor - DNA/RNA Synthesis inhibitor Raltitrexed For research use only.

Raltitrexed

Synonyms: ZD-1694, ICI-D1694, D1694

Raltitrexed (ZD-1694) is a thymidylate synthase inhibitor with an IC50 of 9 nM for the inhibition of L1210 cell growth.

Raltitrexed Chemical Structure

Raltitrexed Chemical Structure

CAS No. 112887-68-0

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Raltitrexed Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human KB cells Cytotoxicity assay 96 h Cytotoxicity against human KB cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay, IC50=5.9 nM 25234128
PC43-10 cells Function assay 96 h Inhibition of RFC (unknown origin) expressed in Chinese hamster PC43-10 cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay, IC50=6.3 nM 25234128
L1210 cell line Growth inhibition assay Growth inhibition of murine tumor L1210 cell line, IC50=9 nM 10508430
human IGROV1 cells Proliferation assay Antiproliferative activity against human RFC and FRalpha expressing human IGROV1 cells, IC50=12.6 nM 18680275
RT16 cells Proliferation assay 96 h Antiproliferative activity against chinese hamster RT16 cells expressing human FRalpha assessed as reduction of viable cells after 96 hrs, IC50=15 nM 21879757
chinese hamster D4 cells Proliferation assay 96 h Antiproliferative activity against chinese hamster D4 cells expressing human FRbeta assessed as reduction of viable cells after 96 hrs, IC50=22 nM 21879757
human KB cells Cytotoxicity assay 200 nM 96 h Cytotoxicity against human KB cells assessed as cell growth inhibition incubated up to 96 hrs in presence of 200 nM folic acid by Celltiter-blue cell viability assay, IC50=22 nM 25234128
R2/PCFT4 cells Function assay 96 h Inhibition of PCFT (unknown origin) expressed in Chinese hamster R2/PCFT4 cells assessed as cell growth inhibition incubated up to 96 hrs by Celltiter-blue cell viability assay, IC50=0.0995 μM 25234128
R2 cells Cytotoxicity assay 96 h Cytotoxicity against chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTitre-Blue fluorescence assay 24256410
R2 cells Growth inhibition assay 96 h Growth inhibition of Chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTiter-blue assay, IC50=0.0995 μM 24111942
L1210 mouse leukemia cells Function assay Compound was evaluated for inhibition of thymidylate synthase, partially purified from L1210 mouse leukemia cells that overproduce thymidylate synthase due to amplification of TS gene, Ki=0.418 μM 1372358
human HepG2 cells Cytotoxicity assay 48 h Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, IC50=1.3 μM 23490159
SGC7901 cells Cytotoxicity assay 48 h Cytotoxicity against human SGC7901 cells after 48 hrs by MTT assay, IC50=8.7 μM 23490159
MCF7 cells Cytotoxicity assay 48 h Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay, IC50=12.6 μM 23490159
Click to View More Cell Line Experimental Data

Biological Activity

Description Raltitrexed (ZD-1694) is a thymidylate synthase inhibitor with an IC50 of 9 nM for the inhibition of L1210 cell growth.
In vitro
In vitro 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. [1] 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. [2] Raltitrexed combined with SN-38 results in synergistic cytotoxicity at broad dose-effect ranges in human colon cancer cells. [3] 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. [4] 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. [5] 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. [6]
Experimental Result Images Methods Biomarkers Images PMID
Growth inhibition assay Cell viability 30820189
Western blot Cleaved caspase-3 / Bax 30820189
In Vivo
In vivo Raltitrexed could be directly transported into the brain via the olfactory pathway in rats. [4]
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02618356 Unknown status
Metastatic Colon Cancer
Fudan University
 December 25 2015 Phase 2
NCT02821559 Completed
Metastatic Colorectal Cancer
Centre Hospitalier Universitaire de Besancon|Hospira now a wholly owned subsidiary of Pfizer
 July 2012 Phase 2

Chemical Information & Solubility

Molecular Weight 458.49 Formula

C21H22N4O6S
CAS No. 112887-68-0 SDF Download Raltitrexed SDF
Smiles CC1=NC2=C(C=C(C=C2)CN(C)C3=CC=C(S3)C(=O)NC(CCC(=O)O)C(=O)O)C(=O)N1
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 92 mg/mL ( (200.65 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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