Table 2.

Drugs targeting one-carbon metabolism in cancer.

Name/Commercial name	Target(s)	Mechanism of action and effect in cells	Status	Cancer Type	Refs.
SHIN1	SHMT1/2	Competitive inhibitor; reduces proliferation by inhibiting glycine and me-THF generation	Preclinical	Various human cancer cell lines	(Ducker et al., 2017)
AGF347	SHMT1/2, GART, ATIC	NA; reduces proliferation by inhibiting glycine and me-THF generation	Preclinical	NSCLC, colon, pancreatic	(Dekhne et al., 2019)
2.12	SHMT1/2	Competitive inhibitor; induces apoptosis, cell cycle arrest, and uracil incorporation into DNA	Preclinical	Lung cancer	(Marani et al., 2016)
LY345899	MTHFD2	Competitive inhibitor; induces apoptosis through reduced mitochondrial NADP(H) generation	Preclinical	Colorectal	(Gustafsson et al., 2017; Ju et al., 2019)
Carolacton	MTHFD1/2	Inhibition of both substrate and cofactor binding in active site; inhibits cell proliferation by an unknown mechanism	Preclinical	Colon, endocervical cancer cell lines	(Fu et al., 2017)
LY231514/MTA/Pemetrexed	TYMS, DHFR, GART, ATIC	Competitive inhibitor; inhibits cell proliferation by limiting thymidylate for DNA synthesis	Approved	Various solid and hematological tumors	(Chattopadhyay et al., 2007; Shih et al., 1997)
Amethopterin/MTX/Methotrexate	TYMS, DHFR	Competitive inhibitor (folate analog); induces cell death by depleting THF levels	Approved	Various solid and hematological tumors	(Kremer, 2004)
5-FU	TYMS	Suicide complex agent; prevents DNA synthesis by blocking conversion of dUMP to dTMP	Approved	Various solid and hematological tumors	(Danenberg, 1977)