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Ribonucleotide reductase (RNR) inhibitors block the enzyme that converts ribonucleotides into deoxyribonucleotides. RNR provides the only de novo route to the deoxyribonucleoside triphosphates (dNTPs) needed for DNA replication and repair. The mammalian enzyme combines the catalytic subunit M1 (RRM1) with the regulatory subunit M2 (RRM2), which holds a tyrosyl radical required for catalysis. Triapine, a heterocyclic thiosemicarbazone characterized in 2000, inhibits RNR activity and is widely used as a reference inhibitor. Didox, amidox and trimidox are polyhydroxy-substituted benzohydroxamic acid and benzamidoxime derivatives that act on the same enzyme. Tezacitabine is a deoxycytidine analog that inhibits RNR after intracellular phosphorylation. COH29 and COH1 are further small-molecule RNR inhibitors for studies of nucleotide metabolism and replication stress.
Synonyms: 3-AP
Triapine is a potent ribonucleotide reductase inhibitor with broad spectrum antitumor activity by inhibiting DNA synthesis.
Didox is a strong inhibitor of ribonucleotide reductase (RR) that interferes with DNA synthesis and repair by blocking the production of deoxyribonucleotides and has demonstrated antitumor effects for decades.
COH29 is a potent ribonucleotide reductase (RNR) inhibitor with anticancer activity.
Tezacitabine is a nucleoside analogue that functions as an irreversible inhibitor of ribonucleotide reductase, disrupting DNA replication and repair processes. This cytostatic and cytotoxic antimetabolite effectively induces apoptosis in target cells. Tezacitabine shows promise in the treatment of leukemias as well as various solid tumors, including carcinomas, making it a valuable compound for cancer research and therapeutic applications.
Tezacitabine hydrate is a potent ribonucleotide reductase inhibitor that exhibits both cytostatic and cytotoxic properties as a nucleoside analogue. By irreversibly inhibiting ribonucleotide reductase, it disrupts DNA replication and repair processes, effectively inducing apoptosis in target cells. Tezacitabine hydrate shows promise for therapeutic applications in the treatment of leukemias and various solid tumors, including carcinomas.
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Amidox is a ribonucleotide reductase inhibitor that interferes with nucleotide metabolism. It enhances the efficacy of Arabinofuranosylcytosine, making it a valuable tool in leukemia research. This compound is essential for studying the biochemical pathways associated with ribonucleotide reduction and potential therapeutic strategies in cancer treatment.
NSAH is a reversible and competitive inhibitor of ribonucleotide reductase (RR), demonstrating a cell-free IC50 of 32 µM and a cell-based IC50 of approximately 250 nM. This compound specifically targets the RR enzyme, which is crucial for DNA synthesis and cellular proliferation. NSAH is valuable for research applications aimed at investigating the role of ribonucleotide reductase in cancer biology and its potential as a therapeutic target.
Synonyms: VF-233 hydrochloride
Trimidox hydrochloride is a potent ribonucleotide reductase inhibitor, demonstrating significant antileukemic activity. This compound effectively inhibits the proliferation of human promyelocytic leukemia HL-60 cells, exhibiting an IC50 of 35 μM. It serves as a valuable research tool for studying ribonucleotide metabolism and its implications in leukemia treatment strategies.
COH1 is a potent inhibitor of ribonucleotide reductase (RR), an essential enzyme in the de novo synthesis of nucleotides. By inhibiting RR, COH1 can impede DNA synthesis, making it a valuable tool in cancer research, as well as studies of mitochondrial disorders and neurodegenerative diseases. Its utility in these areas highlights its role in exploring therapeutic strategies that target nucleotide metabolism.
Synonyms: VF-233
Trimidox is a selective ribonucleotide reductase inhibitor known for its antileukemic properties. It effectively inhibits the proliferation of human promyelocytic leukemia HL-60 cells, exhibiting an IC50 value of 35 μM. This compound is valuable for researchers investigating therapeutic strategies for leukemia and related hematological malignancies.
Synonyms: N3dUrd
2'-Azido-2'-deoxyuridine is a ribonucleotide reductase inhibitor that exhibits significant anti-cancer activity. This compound serves as a versatile click chemistry reagent due to its azide functionality, enabling it to participate in copper-catalyzed azide-alkyne cycloaddition (CuAAc) with alkyne-containing molecules. Additionally, it can facilitate strain-promoted alkyne-azide cycloaddition (SPAAC) reactions with entities featuring DBCO or BCN groups, making it valuable for a range of biochemical applications.
Synonyms: NSC-253272
Caracemide is a ribonucleotide reductase inhibitor derived from hydroxamic acid. It exhibits significant biological activity as an anticancer agent and has been shown to produce severe central nervous system (CNS) toxicity. This compound is of particular interest for research applications focused on cancer therapeutics and the investigation of enzyme inhibition mechanisms.
Synonyms: 3-AP hydrochloride; PAN-811 hydrochloride; OCX191 hydrochloride
Triapine hydrochloride is a potent inhibitor of the M2 subunit of ribonucleotide reductase (RR). This compound exhibits significant biological activity as a radiosensitizer, enhancing the effects of radiation therapy in cancer treatment. Given its mechanism of action, Triapine hydrochloride is useful in cancer research, particularly in studies assessing the modulation of nucleotide metabolism and the efficacy of radiotherapy.
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GTI 2040 is a 20-mer phosphorothioate oligonucleotide that targets the mRNA of human ribonucleotide reductase R2. This reagent effectively downregulates R2 expression, leading to the inhibition of proliferation in human cancer cells in vitro. Additionally, GTI 2040 has demonstrated significant tumor growth inhibition in murine xenograft models of human cancer, making it a valuable tool for cancer research and therapeutic studies.
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VF-149 is a potent ribonucleotide reductase inhibitor that demonstrates significant activity against Plasmodium falciparum, with an IC50 of 6.4 μM. This compound exhibits both antimalarial and antitumor properties, making it a valuable tool for research in the fields of infectious diseases and oncology. VF-149 is suitable for studies focused on malaria infections and cancer biology.
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(E/Z)-NSAH is a reversible, competitive inhibitor of ribonucleotide reductase (RR). This compound exhibits a cell-free IC50 of 32 μM and a cell-based IC50 of approximately 250 nM, making it a valuable tool for studying nucleotide metabolism and cellular proliferation. Its ability to inhibit RR positions it as a significant reagent for research in cancer biology and antiviral therapies, where modulation of nucleotide pools is critical.
YZ51 is a potent ribonucleotide reductase (RR) inhibitor exhibiting enhanced anti-HBV activity compared to its parent compound Osalmid. With an IC50 value of 0.6 μM against recombinant RR activity and 23.7 μM against HepG2.2.15 cell-derived RR activity, YZ51 serves as a valuable tool for investigating the role of RR in viral replication dynamics. This compound can aid research in virology and therapeutic approaches to hepatitis B virus infections.
