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Antifolate C2 is an anti-folate compound that has inhibitory effects on the proliferation of non-squamous non-small cell lung cancer (NS-NSCLC). Antifolate C2 achieves tumor selectivity by targeting proton-coupled folate transporter (PCFT), which is more selective to PCFT than the commonly used anti-folate drug Pemetrexed. Antifolate C2 blocks the biosynthesis of deoxypurine nucleotides by inhibiting glycinamide ribonucleotide formyltransferase ( GARFTase ), ultimately inhibiting the proliferation of tumor cells. Antifolate C2 can be used in studies of NS-NSCLC, especially in patients who do not respond well to Pemetrexed.