Table 1.

Diversity of mechanisms of action and clinical activities of nucleoside and nucleobase analogs.

Predominant mechanism	Drug	Clinical activity
Inhibition of DNA replication	Cytarabine	AML
	Nelarabine	T-ALL
Inhibition of ribonucleotide reductase & DNA replication	Fludarabine	B-cell malignancies, AML
	Cladribine	Hairy cell leukemia
	Gemcitabine	Solid tumor
	Clofarabine	AML, ALL
Activation of DNA MMR to futile cycling	6-Thioguanine	ALL, AML
	6-Mercaptopurine	ALL
Block thymidylate synthase	5-Fluorouracil	Solid tumors
Epigenetic modification	Azacitidine	MDS
	Decitabine	MDS
Mimic genetic syndromes	Pentostatin	Hairy cell leukemia
		B-cell malignancies
RNA incorporation may have a role	Fludarabine	B-cell malignancies
	Azacitidine	MDS
DNA strand breaks	Sapacitabine/CNDAC	AML, MDS, etc.

AML: Acute myeloid leukemia; CNDAC: 2′-C-cyano-2′-deoxy-1-β-D-arabino-pentofuranosylcytosine; MDS: Myelodysplastic syndrome; MMR: mismatch repair; T-ALL: T-cell acute lymphocytic leukemia.