Ribonucleotide reductase inhibitor

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Ribonucleotide reductase inhibitors are a family of anti-cancer drugs that interfere with the growth of tumor cells by blocking the formation of deoxyribonucleotides (building blocks of DNA).

Examples include:

motexafin gadolinium.^[1]
hydroxyurea^[2]
fludarabine, cladribine, gemcitabine, tezacitabine, and triapine^[3]
gallium maltolate, gallium nitrate^[4]

References

^ Zahedi Avval F, Berndt C, Pramanik A, Holmgren A (January 2009). "Mechanism of inhibition of ribonucleotide reductase with motexafin gadolinium (MGd)". Biochem. Biophys. Res. Commun. 379 (3): 775–9. doi:10.1016/j.bbrc.2008.12.128. PMID 19121624. http://linkinghub.elsevier.com/retrieve/pii/S0006-291X(08)02551-5.
^ Mayhew CN, Phillips JD, Cibull ML, Elford HL, Gallicchio VS (September 2002). "Short-term treatment with novel ribonucleotide reductase inhibitors Trimidox and Didox reverses late-stage murine retrovirus-induced lymphoproliferative disease with less bone marrow toxicity than hydroxyurea". Antivir. Chem. Chemother. 13 (5): 305–14. PMID 12630679.
^ Tsimberidou AM, Alvarado Y, Giles FJ (August 2002). "Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies". Expert Rev Anticancer Ther 2 (4): 437–48. doi:10.1586/14737140.2.4.437. PMID 12647987. http://www.future-drugs.com/doi/abs/10.1586/14737140.2.4.437?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov.
^ Bernstein LR (1998). "Mechanisms of therapeutic activity for gallium". Pharmacol. Rev. 50 (4): 665–682. PMID 9860806. http://pharmrev.aspetjournals.org/cgi/reprint/50/4/665.pdf.

External links

Ribonucleotide reductase inhibitor entry in the public domain NCI Dictionary of Cancer Terms

This article incorporates public domain material from the U.S. National Cancer Institute document "Dictionary of Cancer Terms".

Pharmacology: enzyme inhibition

Class

Competitive inhibition · Uncompetitive inhibition · Non-competitive inhibition · Suicide inhibition · Mixed inhibition

Substrate

Oxidoreductase (EC 1)	1.1 Aldose reductase · HMG-CoA reductase 1.3 5-alpha-reductase 1.4 Monoamine oxidase 1.5 Dihydrofolate reductase 1.13 Lipoxygenase 1.14 Aromatase · COX-2 1.17 Xanthine oxidase · Ribonucleotide reductase

Transferase (EC 2)	2.1 COMT · Thymidylate synthase 2.4 PARP 2.5 Dihydropteroate synthetase · Farnesyltransferase 2.6 GABA transaminase 2.7 Nucleotidyltransferase (Integrase, Reverse transcriptase) · Protein kinase (Tyrosine-kinase (Janus kinase))

Hydrolase (EC 3)	3.1 Phosphodiesterase · Acetylcholinesterase · Ribonuclease 3.2 Polygalacturonase · Neuraminidase · Alpha-glucosidase 3.4 Protease: Exopeptidase (Dipeptidyl peptidase-4, ACE) · Endopeptidase (Trypsin, Renin, Matrix metalloproteinase) 3.5 Histone deacetylase · Beta-lactamase

Lyase (EC 4)	4.1 Dopa decarboxylase 4.2 Carbonic anhydrase

Intracellular chemotherapeutic agents/antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine)

Block microtubule disassembly	Taxanes (Cabazitaxel, Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) • Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	dihydrofolate reductase inhibitor (Aminopterin, Methotrexate, Pemetrexed, Pralatrexate) • thymidylate synthase inhibitor (Raltitrexed, Pemetrexed)

Purine	adenosine deaminase inhibitor (Pentostatin) halogenated/ribonucleotide reductase inhibitors (Cladribine, Clofarabine, Fludarabine) thiopurine (Thioguanine, Mercaptopurine)

Pyrimidine	thymidylate synthase inhibitor (Fluorouracil, Capecitabine, Tegafur, Carmofur, Floxuridine) DNA polymerase inhibitor (Cytarabine) ribonucleotide reductase inhibitor (Gemcitabine) hypomethylating agent (Azacitidine, Decitabine)

Deoxyribonucleotide	ribonucleotide reductase inhibitor (Hydroxycarbamide)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan)

II	Podophyllum (Etoposide, Teniposide)

II+Intercalation	Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin, Pirarubicin, Valrubicin, Zorubicin) • Anthracenediones (Mitoxantrone, Pixantrone)

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Mechlorethamine • Cyclophosphamide (Ifosfamide, Trofosfamide) • Chlorambucil (Melphalan, Prednimustine) • Bendamustine • Uramustine • Estramustine Nitrosoureas: Carmustine • Lomustine (Semustine) • Fotemustine • Nimustine • Ranimustine • Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan, Treosulfan) Aziridines: Carboquone • ThioTEPA • Triaziquone • Triethylenemelamine

Alkylating-like	Platinum (Carboplatin, Cisplatin, Nedaplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin)

Nonclassical	Hydrazines (Procarbazine) • Triazenes (Dacarbazine, Temozolomide) • Altretamine • Mitobronitol

Intercalation	Streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin)

Photosensitizers/PDT

Aminolevulinic acid/Methyl aminolevulinate • Efaproxiral • Porphyrin derivatives (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin)

Other

Enzyme inhibitors	FI (Tipifarnib) • CDK inhibitors (Alvocidib, Seliciclib) • PrI (Bortezomib) • PhI (Anagrelide) • IMPDI (Tiazofurine) • LI (Masoprocol) • PARP inhibitor (Olaparib) • HDAC (Vorinostat, Romidepsin)

Receptor antagonists	ERA (Atrasentan) • retinoid X receptor (Bexarotene) • sex steroid (Testolactone)

Other/ungrouped	Amsacrine • Trabectedin • retinoids (Alitretinoin, Tretinoin) • Arsenic trioxide • asparagine depleters (Asparaginase/Pegaspargase) • Celecoxib • Demecolcine • Elesclomol • Elsamitrucin • Etoglucid • Lonidamine • HAMLET (human alpha-lactalbumin made lethal to tumor cells) • Lucanthone • Mitoguazone • Mitotane • Oblimersen • Omacetaxine mepesuccinate • mTOR inhibitors (Everolimus, Temsirolimus)

M: NEO

tsoc, mrkr

tumr, epon, para

drug (L1i/1e/V03)

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