Pemetrexed

SKU: orb1310854

Description

Pemetrexed

Research Area

Cell Biology, Metabolism Research, Molecular Biology, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 137281-23-3
• MW: 427.41
• Purity: 98.10% (May vary between batches)
• Formula: C₂₀H₂₁N₅O₆
• SMILES: Nc1nc(=O)c2c(CCc3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)c[nH]c2[nH]1
• Target: Autophagy,DNA/RNA Synthesis,DHFR,Antifolate
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.68 mM);DMSO:35 mg/mL (81.89 mM)

Bioactivity

• Target IC50:
  TS:1.3 nM(ki)|DHFR:7.2 nM(ki)|GARFT:65 nM(ki)
• In Vivo:
  The group of mice treated with PC61 combined with Pemetrexed exhibited significantly longer survival compared to those treated with PC61 alone, rat IgG combined with Pemetrexed, or left untreated. Survival analysis further confirmed that the PC61 and Pemetrexed combination resulted in significantly improved survival rates .
• In Vitro:
  Pemetrexed (LY231514) disodium is a novel classical antifolate whose antitumor activity likely results from the simultaneous inhibition of several key folate-requiring enzymes via its polyglutamated metabolites. It is one of the best substrates for the enzyme FPGS (Km=1.6 μM, Vmax/Km=621). Polyglutamation and the polyglutamated metabolites of LY231514 play significant roles in determining its selectivity and antitumor activity. LY231514 only moderately inhibits TS (Ki=340 nM, recombinant mouse), but its pentaglutamate form is 100-fold more potent (Ki=3.4 nM), making it one of the most potent folate-based TS inhibitors.
• Cell Research:
  Pemetrexed is dissolved in DMSO and stored, and then diluted with cell culture medium before use. Dose-response curves are generated to determine the concentration required for 50% inhibition of growth (IC50). Pemetrexed is dissolved initially in DMSO at a concentration of 4 mg/mL and further diluted with cell culture medium to the desired concentration. CCRF-CEM leukemia cells in complete medium are added to 24-well Cluster plates at a final concentration of 4.8×l04 cells/well in a total volume of 2 mL. Test compounds at various concentrations are added to duplicate wells so that the final volume of DMSO is 0.5%. The plates are incubated for 72 h at 37°C in an atmosphere of 5% CO2 in air. At the end of the incubation, cell numbers are determined on a ZBI Coulter counter. Control wells usually contain 4×105 to 6×105 cells at the end of the incubation. For several studies, IC50s are determined for each compound in the presence of either 300 μM AICA, 5 μM thymidine, 100 μM hypoxanthine, or combination of 5 μM hymidine plus 100 μM hypoxanthine.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LY-231514 Disodium Hydrate, LY231514, LY231514 Disodium Hydrate, GARFT, Autophagy, Antifolate, DNASynthesis, DHFR, DNA Synthesis, Thymidylate synthase, Pemetrexed acid, RNASynthesis, RNA Synthesis

Compound Identifiers

PubChem CID

135410875