Pemetrexed-13C5 (sodium salt hydrate)

Pemetrexed-13C5 is intended for use as an internal standard for the quantification of pemetrexed (Cay-14269) by GC- or LC-MS. Pemetrexed is an antifolate with anticancer activity. It is an inhibitor of folate-dependent enzymes involved in purine synthesis, including thymidylate synthase and dihydrofolate reductase (Kis = 109 and 7 nM, respectively, for the human recombinant enzymes), and the potency for thymidylate kinase is increased following polyglutamination of pemetrexed (Ki = 1.3 nM for pemetrexed-glu5). Pemetrexed is an inhibitor of other nucleotide metabolism enzymes in a polyglutamination-dependent manner, including glycinamide ribonucleotide formyltransferase, with Ki values of 9,300 and 65 nM for the non-glutaminated and polyglutaminated mouse recombinant enzyme, respectively, and aminoimidazole carboxamide ribonucleotide formyltransferase, with Ki values of 3,600 and 265 nM for the non-glutaminated and polyglutaminated human enzyme, respectively. It inhibits proliferation of CCRF-CEM cells but not 5,10-dideazatetrahydrofolate-resistant CR15 cells (IC50s = 0.254 and 200 µM, respectively). Pemetrexed (100 mg/kg, i.p.) reduces tumor growth in A549, H1299, and PC-9 non-small cell lung cancer cell (NSCLC) mouse xenograft models but not in models using the same cell lines overexpressing thymidylate kinase.Formal Name: N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid-13C5, disodium salt, heptahydrate. Molecular Formula: C15[13C]5H19N5O6 . 2Na [7H2O]. Formula Weight: 602.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: slightly soluble, Water: slightly soluble. SMILES: O=C(N[13C@H]([13C]([O-])=O)[13CH2][13CH2][13C]([O-])=O)C(C=C1)=CC=C1CCC2=CNC(NC(N)=N3)=C2C3=O.[Na+].[Na+].O.O.O.O.O.O.O. InChi Code: InChI=1S/C20H21N5O6.2Na.7H2O/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27,,,,,,,,,/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29),,,7*1H2/q,2*+1,,,,,,,/p-2/t13-,,,,,,,,,/m0........./s1/i7+1,8+1,13+1,14+1,19+1,,,,,,,,,. InChi Key: QJVSMHJWAOSBMD-RGMGAWIKSA-L.