Table 2 Clinically FDA-approved drugs targeting nucleotide metabolism in cancer

Mercaptopurine

Hypoxanthine–guanine phosphoribosyltransferase, amidophosphoribosyltransferase, Inosine-5'-monophosphate dehydrogenase

Acute lymphatic leukemia

1953

[112, 113]

Methotrexate

Dihydrofolate reductase, thymidylate synthase, aminoimidazole carboxamide ribonucleotide transformylase, and amido phosphoribosyltransferase

Acute lymphoblastic leukemia, gestational choriocarcinoma, chorioadenoma destruens, hydatidiform mole, breast cancer, epidermoid cancer of the head and neck, advanced mycosis fungoides, lung cancer, and advanced non-Hodgkin’s lymphoma

1953

[114]

Fluorouracil

Thymidylate synthase

Colon, esophageal, gastric, rectum, breast, biliary tract, stomach, head and neck, cervical, pancreas and renal cell cancer

1962

[108]

Thioguanine

DNA

Acute non-lymphocytic leukemias

1966

[113, 115]

Cytarabine

DNA polymerase

Acute non-lymphocytic leukemia

1969

[116]

Floxuridine

Thymidylate synthase

Gastrointestinal adenocarcinoma, liver cancer

1970

[117, 118]

Cisplatin

DNA

Testicular tumors, ovarian tumors and bladder cancer

1978

[119]

Carboplatin

DNA

Advanced ovarian carcinoma

1989

[120]

Fludarabine

Ribonucleoside-diphosphate reductase large subunit, DNA polymerase alpha catalytic subunit

Chronic lymphocytic leukemia

1991

[121, 122]

Cladribine

Ribonucleoside-diphosphate reductase, DNA polymerase

Active hairy cell leukemia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma

1991

[123]

Pentostatin

Adenosine deaminase

Hairy cell leukemia

1991

[29]

Hydroxyurea

Ribonucleotide reductase

Acute myeloid leukemia

1995

[124]

Gemcitabine

Ribonucleoside-diphosphate reductase, thymidylate synthase, UMP-CMP kinase

Ovarian, lung, breast and pancreas cancer

1996

[125, 126]

Dacarbazine

Unspecific, DNA synthesis

Malignant melanoma, Hodgkin’s disease

1998

[127]

Capecitabine

Thymidylate synthase

Breast and colon cancer

1998

[128]

Clofarabine

Ribonucleoside-diphosphate reductase, DNA polymerase

Acute lymphocytic leukemia

2004

[129, 130]

Azacytidine

Cysteine and methionine metabolism

Chronic myelomonocytic leukemia

2004

[131, 132]

Nelarabine

Ara-G triphosphate

Acute T-cell lymphoblastic leukemia, T-cell lymphoblastic lymphoma

2005

[133]

Decitabine

DNA (cytosine-5)-methyltransferase 3A and 3B

Myelodysplastic syndromes (MDS)

2006

[134]

Oxaliplatin

DNA

Colorectal cancer

2009

[120]

Idelalisib

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit

Chronic lymphocytic leukemia, follicular B-cell non-Hodgkin lymphoma, and small lymphocytic lymphoma

2014

[135, 136]

Tipiracil

Thymidine phosphorylase

Colorectal cancer

2015

[137]

Pemetrexed

Thymidylate synthase, Bifunctional purine biosynthesis protein PURH, Dihydrofolate reductase, Trifunctional purine biosynthetic protein adenosine-3

Mesothelioma, NSCLC

2015

[138]