Pemetrexed disodium heptahydrate

Pemetrexed disodium heptahydrate (CAS No.: 357166-29-1) is a synthetic folate antagonist antimetabolite commonly used as a model compound in biomedical research and drug development to simulate the effects of folate pathway blockade and one-carbon metabolism disruption in mammalian systems on nucleotide homeostasis and the integrity of genomic replication; its mechanism of action is mainly mediated by inhibition of multiple folate-dependent target enzymes, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). Biochemical inhibition of these targets is commonly observed in the low nanomolar range, with Ki values of approximately 1.3 nM, 7.2 nM, and 65 nM, respectively, thereby inhibiting de novo thymidylate and purine biosynthesis, leading to depletion of nucleotide pools and secondary impairment of DNA replication and repair; intracellularly, it can undergo polyglutamation, thereby increasing affinity for target enzymes and intracellular retention, enhancing the intensity of pathway inhibition in a cell-context-dependent manner. In terms of in vitro phenotypes, antiproliferative activity in the submicromolar to low micromolar range is typically observed in sensitive models, whereas antifolate-tolerant cell lines often require higher exposure levels. Common functional outcomes include S-phase arrest and programmed cell death, and target-related protein expression profiles and folate metabolic status can significantly influence responsiveness. At the application level, this compound is widely used in mechanistic enzymology experiments, cell proliferation and cell cycle studies, and preclinical models of tumor biology (such as selected non-small cell lung-derived and mesothelioma-derived cells and their xenograft models) to elucidate the biological consequences of nucleotide metabolism pathway inhibition, the determinants of sensitivity and tolerance, and their relationship with driver gene backgrounds; the concentrations or doses used in specific experiments are generally determined according to the research objectives and experimental design, and it is strictly limited to laboratory research use and not intended for human or other non-research applications.