This review will discuss the key preclinical and clinical features of antifolates, from
methotrexate (MTX) to pemetrexed and beyond. Despite 50 years of study, definition of the …

Our current understanding of the mechanisms of action of antitumor agents and the precise
mechanisms underlying drug resistance is that these two processes are directly linked …

Gamma-glutamyl hydrolase (GGH) is a lysosomal enzyme involved in the metabolism of
folates and anti-folates. It acts as an endo-and/or exo-peptidase to cleave gamma …

Nα-(4-Amino-4-deoxypteroyl)-Nδ-hemiphthaloyl-l-ornithine (PT523) is an unusually tight-
binding dihydrofolate reductase (DHFR) inhibitor and is efficiently taken up into cells via the …

Lipophilic methotrexate (MTX)–lipoamino acid conjugates coupled with amide or ester
linkages (1a–1r) were synthesised. The inhibitory activity of the conjugates was evaluated …

N-[4-[1-Methyl-2-(2, 4-diaminofuro [2, 3-d] pyrimidin-5-yl) ethyl] benzoyl]-l-glutamic acid (5)
and its C8-C9 conformationally restricted E-and Z-isomers (6 and 7) were designed and …

Seven novel 2, 4-diamino-5-deaza-6, 7, 8, 9-tetrahydropyrido [3, 4-g] pteridine derivatives
3− 9 with different benzyl and a benzoyl substitution at the N7 position were designed and …

N-[4-[1-Ethyl-2-(2, 4-diaminofuro [2, 3-d] pyrimidin-5-yl) ethyl] benzoyl]-l-glutamic acid 3 was
designed and synthesized to investigate the effect of homologation of a C9-methyl to an …

Folylpoly-γ-glutamate synthetase (FPGS, EC 6.3. 2.17) is an ATP-dependent ligase that
catalyzes formation of poly-γ-glutamate derivatives of reduced folates and antifolates such …

Compounds 2− 5 were designed as potential antifolate nonpolyglutamatable inhibitors of
thymidylate synthase (TS). These analogues are structurally related to 2-amino-4-oxo-5 …