ribonucleotide reductase

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.

Osalmid (Oxaphenamide) is a choleretic drug, inhibits ribonucleotide reductase activity by targeting ribonucleotide reductase small subunit M2 (RRM2).

Cytidine 5'-diphosphate disodium (CDP sodium salt) produces CTP to support DNA and RNA biosynthesis and ribonucleotide reductase to produce dCMP.

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.

3-AP (Triapine) is a novel inhibitor of the M2 subunit of ribonucleotide reductase (RR).

COH29 (RNR Inhibitor COH29) is an orally available, aromatically substituted thiazole and human ribonucleotide reductase (RNR) inhibitor with potential antineoplastic activity. COH29 binds to the ligand-binding pocket of the RNR M2 subunit (hRRM2) near the C-terminal tail, decreasing the pool of deoxyribonucleotide triphosphates needed for DNA synthesis, leading to cell cycle arrest and growth inhibition. It may also inhibit the nuclear enzyme poly (ADP-ribose) polymerase (PARP) 1, preventing DNA repair, causing accumulation of DNA breaks, and inducing apoptosis.

2'-Azido-2'-deoxyuridine (N3dUrd) is a ribonucleotide reductase inhibitor exhibiting anti-cancer activity.

Caracemide (NSC-253272) inhibits the enzyme ribonucleotide reductase of Escherichia coli and can be utilized in anticancer studies.

Gemcitabine elaidate (CP-4126), is a lipophilic, unsaturated fatty acid ester derivative of gemcitabine (dFdC), an antimetabolite deoxynucleoside analogue, with potential antineoplastic activity. Upon hydrolysis intracellularly by esterases, the prodrug gemcitabine is converted into the active metabolites difluorodeoxycytidine di- and tri-phosphate (dFdCDP and dFdCTP) by deoxycytidine kinase. dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and apoptosis.

Guanazole, a triazole-derived antimetabolite, functions as an RNR inhibitor. This compound suppresses mammalian ribonucleotide reductase activity and DNA synthesis by eliminating tyrosyl radicals, thereby exhibiting cytostatic properties.

3-AP-Me is the dimethyl derivative of the ribonucleotide reductase inhibitor 3-AP (SML0568). It activates the endoplasmic reticulum (ER) stress pathway by promoting eIF2α phosphorylation and upregulating gene expression of transcription factors ATF4 and ATF6, thereby inducing apoptosis. Additionally, 3-AP-Me activates cellular stress kinases c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase, leading to the upregulation of spliced mRNA variant XBP1. It is applicable in cancer research.

NSC 641396 is a ribonucleotide reductase (RNR) inhibitor with an IC50 value of 1.2 μM. Additionally, it acts as an inhibitor of protein arginine N-methyltransferase 9 (PRMT9) and exhibits antitumor properties.

GW8510 is a CDK2 (cell cycle protein-dependent kinase 2) inhibitor and RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) inhibitor that affects DNA synthesis and antiproliferation in tumor cells. In mammalian aging models, GW851 improves cognition and prolongs lifespan, which may be related to the modulation of the expression of cell cycle-related protein p21 and CDK family genes, as well as the improvement of mitochondrial function.

YZ51, a novel potent inhibitor of ribonucleotide reductase (RR), inhibits hepatitis B virus replication by targeting ribonucleotide reductase M2 protein.

Fludarabine triphosphate (F-ara-ATP), the cytotoxic metabolite of Fludarabine phosphate, inhibits ribonucleotide reductase and DNA polymerase, ultimately leading to cellular apoptosis.

Tezacitabine is a cytostatic and cytotoxic antimetabolite and a nucleoside analogue with a dual mechanism of action that irreversibly inhibits ribonucleotide reductase and can be incorporated into DNA during replication or repair, causing DNA chain termination. It blocks tumor cells in the G1 and S phases of the cell cycle, inducing apoptotic cell death, with potential applications in treating leukemia and solid tumors[1][2].

Amidox is a ribonucleotide reductase inhibitor.

Fludarabine triphosphate (F-ara-ATP) trisodium, the principal metabolite of Fludarabine, is a potent, noncompetitive, and specific inhibitor of DNA primase with an IC50 value of 2.3 μM and a Ki of 6.1 μM. It obstructs DNA synthesis by hindering DNA primase and primer RNA formation, while also inhibiting ribonucleotide reductase and DNA polymerase activities, effectively inducing cellular apoptosis [1] [2].

Didox (NSC-324360) is a synthetic ribonucleotide reductase (RR) inhibitor shown to reduce oxidative injury markers in the brains of HIV patients with dementia.

Herpes Virus Inhibitor 1 is a compound that inhibits the replication of the herpes virus by disrupting the quaternary structure of its ribonucleotide reductase. This action effectively hinders the virus's ability to replicate [1] [2].

Herpes Virus Inhibitor 2, a compound known for its effectiveness in disrupting the quaternary structure of herpes virus ribonucleotide reductase, functions as a potent inhibitor of viral replication, thereby halting the progression of the herpes virus [1] [2].

COH1 is a ribonucleotide reductase (RR) inhibitor utilized in research pertaining to cancer, mitochondrial diseases, and neurodegenerative disorders [1].

GTI-2040, a 20-mer phosphorothioate oligonucleotide, targets the mRNA sequence of human ribonucleotide reductase R2 for hybridization. This compound inhibits cancer cell proliferation by reducing R2 expression in vitro and markedly suppresses tumor growth in xenograft models of human cancer in mice.

Triapine (hydrochloride), also known as 3-AP or PAN-811, represents the hydrochloride variant of Triapine. This compound serves as a potent inhibitor of the M2 subunit of ribonucleotide reductase (RR) and acts as an effective radiosensitizer [1].