Raltitrexed

SKU: orb1300600

Description

Raltitrexed (D1694) is a potent thymidylate synthase inhibitor with an IC50 of 9 nM, effectively suppressing L1210 leukemia cell growth in vitro. It is widely used in cancer research, including studies on colorectal carcinoma, both in cellular assays and in vivo models.

Research Area

Cell Biology, Molecular Biology

Key Properties

• CAS Number: 112887-68-0
• MW: 458.49
• Purity: 99.29% (May vary between batches)
• Formula: C₂₁H₂₂N₄O₆S
• SMILES: O=C1C=2C(=CC=C(CN(C)C=3SC(C(N[C@@H](CCC(O)=O)C(O)=O)=O)=CC3)C2)NC(C)=N1
• Target: Nucleoside Antimetabolite/Analog,DNA/RNA Synthesis
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (8.72 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:123 mg/mL (268.27 mM)

Bioactivity

• Target IC50:
  TS:9 nM
• In Vivo:
  Raltitrexed can be transported directly into the brain through the olfactory pathway in rats.
• In Vitro:
  Raltitrexed induces double-stranded DNA breaks in a concentration-dependent manner. In Lovo cells and LS174T cell lines containing wild-type p53, Raltitrexed increases the levels of the Bax protein up to 5-fold. In human colon cancer cells, Raltitrexed is actively absorbed into cells and is then rapidly and extensively metabolized into a series of polyglutamates, which results in the effective inhibition of thymidylate synthase. Raltitrexed is delivered to the brain very quickly and can be detected in all brain tissues within 5 minutes. In human colon cancer cells, the combination of Raltitrexed and SN-38 results in a synergistic cytotoxic effect within a range of concentrations. Raltitrexed is a specific folate-based inhibitor of thymidylate synthase. The effect on the activity of advanced rectal cancer is similar to fluorouracil (5-fluorouracil) plus leucovorin. Raltitrexed produces activity by rapid cell entry and glutamination. The glutaminated derivatives are more than 100 times more active than the parent compound. In the HCT-8 cell line, Raltitrexed results in an increase in intracellular phosphoribosyl pyrophosphate (PRPD) indicating that the cytotoxic effect of Raltitrexed in combination with 5-FU is due to increased nucleotide formation of 5-FU. Combinations of Raltitrexed and folinic acid (5FU-FA) show a combination of mode-dependent, synergistic inhibition of proliferation, which is determined by measuring the combination series. Raltitrexed combined with Vorinostat produced significant synergistic effects of cell cycle perturbation and S-phase arrest.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Nucleoside Antimetabolite, NucleosideAntimetabolite, Nucleoside Antimetabolite/Analog, Inhibitor, ICI-D 1694, ICI-D1694, ICI-D-1694, Analog, DNASynthesis, DNA Synthesis, D 1694, D1694, D-1694, Thymidylate Synthase, Thymidylate synthase, Raltitrexed, ZD 1694, ZD1694, ZD-1694, Tomudex, RNA Synthesis, RNASynthesis

Compound Identifiers

PubChem CID

135400182