Nucleoside Antimetabolite/Analog

Gemcitabine (LY188011) is a synthetic cytosine nucleoside derivative and an inhibitor of DNA synthesis. Gemcitabine has antitumor and antimetabolic activities. Gemcitabine induces autophagy and apoptosis.

Decitabine (Deoxycytidine) is a deoxycytidine analog, a DNA methyltransferase inhibitor with oral activity. Decitabine has antitumor activity and antimetabolic activity. Decitabine induces cell cycle arrest and apoptosis.

5-BrdU (Broxuridine) , a nucleoside analog, are used in the detection of proliferating cells and competes with thymidine for incorporation into DNA.

5-Fluorouracil (5-FU) is a uracil analog and inhibitor of DNA synthesis, exhibiting antitumor activity by affecting pyrimidine synthesis through thymidylate synthase inhibition; it induces apoptosis and autophagy.

Fludarabine (Fludarabinum) is a fluorinated purine analog, an inhibitor of nucleic acid synthesis and an inhibitor of STAT1 activation. Fludarabine has antitumor activity and can be used for the treatment of leukemia and lymphoma.

Sangivamycin (NSC-65346) is an effective inhibitor of protein kinase C (PKC, Ki = 10 μM). Sangivamycin exhibits antiproliferative activity against a variety of human cancers.

Gemcitabine hydrochloride (LY 188011 hydrochloride) is a synthetic cytosine nucleoside derivative and an inhibitor of DNA synthesis. Gemcitabine has antitumor and antimetabolic activities. Gemcitabine induces autophagy and apoptosis.

5-Azacytidine (Ladakamycin) is a cytidine nucleoside analog, a DNA methylation inhibitor with specificity. 5-Azacytidine regulates gene expression by decreasing the level of DNA methylation. 5-Azacytidine induces autophagy and has antitumor activity.

2’-Deoxy-N4-methylcytidine (N(3)-Methyl-2'-deoxycytidine) is a purine nucleoside analog with potential antitumor activity for the study of apoptosis.

Rabacfosadine (GS-9219) is a novel dual pre-drug of the acyclic nucleotide phosphonate PMEG to tumor lymphocytes for the study of lymphoma.

LY2334737 is an orally available prodrug of gemcitabine with antineoplastic activity.

Tipiracil hydrochloride (MA-1 hydrochloride) is a thymidine phosphorylase inhibitor (TPI). Tipiracil hydrochloride is one of the active components in TAS-102, which is an anticancer drug candidate currently in clinical trials.

Capecitabine (Capecitibine) is a fluoropyrimidine carbamate belonging to the class of antineoplastic agents called antimetabolites. As a prodrug, capecitabine is selectively activated by tumor cells to its cytotoxic moiety, 5-fluorouracil (5-FU); subsequently, 5-FU is metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP) by both tumor cells and normal cells. FdUMP inhibits DNA synthesis and cell division by reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate for incorporation into the RNA strand.

5-Ethynyluridine is a clickable form of uridine.1It is incorporated into cellular RNA, but not DNA, and has been used to detect transcriptionin vitroandin vivo. 1.Jao, C.Y., and Salic, A.Exploring RNA transcription and turnover in vivo by using click chemistryProc. Natl. Acad. Sci. USA105(41)15779-15784(2008)

Peldesine (BCX 34) is an effective, competitive, reversible, and orally active inhibitor of purine nucleoside phosphorylase. Peldesine inhibits T-cell proliferation with an IC50 of 800 nM. Peldesine can be used in research on cutaneous T-cell lymphoma, psoriasis and HIV infection.

Floxuridine (FUDR) is an antimetabolite, floxuridine inhibits thymidylate synthase, resulting in disruption of DNA synthesis and cytotoxicity.

RX-3117 (fluorocyclopentenylcytosine) is a novel a cytidine analog. RX-3117 displays anticancer activity in several cancer cell lines, including gemcitabine-resistant variants.

N2-Methylguanosine is a modified nucleoside found at several specific sites in various tRNAs.

CNDAC hydrochloride, a nucleoside analog, is a metabolite of the sapacitabine.

Ganciclovir (2'-Nor-2'-deoxyguanosine) is an ACYCLOVIR analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections.

Clofarabine (Clofarex)m, a second generation purine nucleoside analog with antineoplastic activity, inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase.

3-Methylcytidine as biomarkers of four different types of cancer: lung cancer, gastric cancer, colon cancer, and breast cancer.

Dacarbazine (DTIC-Dome) is an antineoplastic agent. It has significant activity against melanomas.

Trifluridine (NSC-75520) is a fluorinated thymidine analog with potential antineoplastic activity. Trifluridine is incorporated into DNA and inhibits thymidylate synthase, resulting in inhibition of DNA synthesis, inhibition of protein synthesis, and apoptosis. This agent also exhibits antiviral activity.

Raltitrexed (D1694)(IC50 of 9 nM), a thymidylate synthase inhibitor, is used for the inhibition of L1210 cell growth.

LNA-Adenosine (LNA-A) is a nucleoside analogue that acts as a ligand for adenosine A3 receptors.

6-Mercaptopurine (6-MP) is an antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.

dGTP (2'-Deoxyguanosine-5'-triphosphate) is a guanosine nucleotide highly susceptible to oxidative damage, resulting in 8-O-GDP, 8-O-dGTP, 8-O-GTP, and 8-O-dGTP.

Carmofur (HCFU) is a highly potent acid ceramidase inhibitor, used in the treatment of breast and colorectal cancer. Carmofur has been known to induce leukoencephalopathy.

Fludarabine Phosphate (NSC 312887 Phosphate) is the phosphate salt of a fluorinated nucleotide antimetabolite analog of the antiviral agent vidarabine (ara-A) with antineoplastic activity. Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite may inhibit DNA polymerase alpha, ribonucleotide reductase, and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth.

2-Thiocytidine is a purine nucleoside analog that targets malignant tumors of the inert lymphatic system and possesses a broad spectrum of antitumor activity. It induces apoptosis by inhibiting DNA synthesis.

Deoxyguanosine triphosphate trisodium salt (2'-Deoxyguanosine-5'-triphosphate trisodium salt) is a nucleotide precursor for DNA synthesis in cells and can be used in the reverse transcription-polymerase chain reaction (RT-PCR) for DNA amplification.

7-Methylxanthine is a methyl derivative of xanthine, the purine component of human urinary calculi.7-Methylxanthine has an affinity for adenosine receptors.7-Methylxanthine is a methyl derivative of xanthine, the purine component of human urinary calculi.7-Methylxanthine has an affinity for adenosine receptors.

Trifluridine tipiracil hydrochloride mixture (TAS-102) is a novel oral combination drug containing trifluridine (TFT) and tipiracil hydrochloride (TTP) in a 2:1 molar ratio.

N6-Methyl-2'-O-methyladenosine (N6,2′-O-Dimethyladenosine), a substrate for adiposity and obesity-related genes (FTO), is a reversible modifier compound found on a wide variety of RNA molecules.N6,2′-O-Dimethyladenosine can be used to study obesity and its related diseases.

6-Thioinosine (6TI) is a purine antimetabolite, acts as an anti-adipogenesis agent.

Isoguanine, a purine base and isomer of guanine, serves as a building block in organic synthesis.

7-Methylguanosine is a novel cNIIIB nucleotidase inhibitor with an IC50 of 87.8 ± 7.5 μM.

Sapacitabine (CS682) is an orally available nucleoside analog precursor compound with potential anti-tumor activity for the study of acute myeloid leukemia.

Deoxycytidine triphosphate trisodium salt (2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE TRISODI) contributes to antibiotic lethality in stationary-phase mycobacteria.

Nelarabine (GW 506U78) is a purine nucleoside analog and DNA synthesis inhibitor with IC50 from 0.067-2.15 μM in tumor cells.

Deoxycytidine triphosphate is a nucleoside triphosphate.It is a raw material in DNA synthesis. Deoxycytidine triphosphate has many applications, such as real-time PCR, cDNA synthesis, and DNA sequencing.

1-Methylcytosine (4-amino-1-methylpyrimidin-2(1H)-one) is a methylated form of the cytosine and can be used as the nucleobase of hachimoji DNA paired with isoguanine.

8-Azahypoxanthine (NSC-22709) inhibits hypoxanthine-guanine-xanthine phosphoribosyltransferase and has antimalarial properties.

N6,N6-Dimethyladenosine is find in mycobacterium bovis Bacille Calmette-Guérin tRNA.

5-Hydroxyuridine (OHUrd) is a purine nucleoside analogue with potential antitumor activity, demonstrating cytotoxicity against human colon adenocarcinoma cell lines.

Ara-G is an analog of the nucleoside guanosine and an active metabolite of nelarabine .1,2 Ara-G accumulates in T lymphoblasts and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into the DNA.3,1 Ara-G inhibits DNA replication by 92% after 30 minutes when used at a concentration of 50 μM in CEM cells, which are used as a model for human T lymphoblasts.1 It also halts the cell cycle at the sub-G1 phase and induces apoptosis in CEM cells.3 Syngeneic bone marrow containing 6C3HED tumor cells treated with ara-G (100 mM) ex vivo prior to transplantation increases survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.4References1. Leanza, L., Miazzi, C., Ferraro, P., et al. Activation of guanine-β-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints. Exp. Cell Res. 316(20), 3443-3453 (2010).2. Lambe, C.U., Averett, D.R., Paff, M.T., et al. 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res. 55(15), 3352-3356 (1995).3. Rodriguez, C.O., Jr., Stellrecht, C.M., and Gandhi, V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 102(5), 1842-1848 (2003).4. Kurtzberg, J. Guanine arabinoside as a bone marrow-purging agent. Ann. N.Y. Acad. Sci 685(1), 225-236 (1993). Ara-G is an analog of the nucleoside guanosine and an active metabolite of nelarabine .1,2 Ara-G accumulates in T lymphoblasts and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into the DNA.3,1 Ara-G inhibits DNA replication by 92% after 30 minutes when used at a concentration of 50 μM in CEM cells, which are used as a model for human T lymphoblasts.1 It also halts the cell cycle at the sub-G1 phase and induces apoptosis in CEM cells.3 Syngeneic bone marrow containing 6C3HED tumor cells treated with ara-G (100 mM) ex vivo prior to transplantation increases survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.4 References1. Leanza, L., Miazzi, C., Ferraro, P., et al. Activation of guanine-β-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints. Exp. Cell Res. 316(20), 3443-3453 (2010).2. Lambe, C.U., Averett, D.R., Paff, M.T., et al. 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res. 55(15), 3352-3356 (1995).3. Rodriguez, C.O., Jr., Stellrecht, C.M., and Gandhi, V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 102(5), 1842-1848 (2003).4. Kurtzberg, J. Guanine arabinoside as a bone marrow-purging agent. Ann. N.Y. Acad. Sci 685(1), 225-236 (1993).

2'-OMe-Guanosine is a modified nucleoside produced by the action of tRNA guanosine-2'-o-methyltransferase. 2'-OMe-Guanosine has a certain pro-apoptotic effect.