Pemetrexed is a novel antifolate and antimetabolite for TS, DHFR and GARFT with Ki of 1.3 nM, 7.2 nM and 65 nM, respectively.
IC50 Value: 1.3nM(Ki for TS); 7.2nM(DHFR); 65nM(GARFT)
Target: Antifolate
in vitro: The Ki values of the pentaglutamate of LY231514 are 1.3, 7.2, and 65 nM for inhibition against TS, DHFR, and GARFT, respectively. In contrast, although a similar high level of inhibitory potency was observed for the parent monoglutamate against DHFR (7.0 nM), the inhibition constants (Ki) for the parent monoglutamate are significantly weaker for TS (109 nM) and GARFT(9,300 nM).The parent monoglutamate LY231514 inhibited rhTS with a Ki of 109 nM when the monoglutamated form of the substrate (6R-MTHF) (6[R]-5,l0-meth ylenetetrahydrofolate) was used. This is in good agreement with the Ki value generated earlier for rmTS (Ki= 340 nM)
in vivo: pemetrexed effectively reduces kidney uptake of radiofolates not only in xenografted mice but also ina syngeneic tumor mouse model
Clinical trail: Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer is reported

Antifolate
Calcium N5-methyltetrahydrofolate
Folinic acid
Leucovorin Calcium
Levoleucovorin Calcium
Levomefolate calcium
Levomefolic acid
Methotrexate
Pralatrexate
Pyrimethamine
Trimethoprim