Target Information

Target General Infomation
Target ID
T38301
Former ID
TTDS00421
Target Name
Ribonucleoside-diphosphatereductase subunit M2
Gene Name
RRM2
Synonyms
RR2; Ribonucleotide reductase small chain; Ribonucleotide reductase small subunit; RRM2
Target Type
Successful
Disease Chronic myelogenous leukaemia [ICD9: 205.1; ICD10: C92.1]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Gastric cancer [ICD9: 151; ICD10: C16]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Metastatic pancreatic [ICD10: C25.9]
Nerve injury [ICD10: T14.4]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling.
BioChemical Class
Oxidoreductases acting on CH or CH(2) groups
Target Validation
T38301
UniProt ID
P31350
EC Number
EC 1.17.4.1
Sequence
MLSLRVPLAPITDPQQLQLSPLKGLSLVDKENTPPALSGTRVLASKTARRIFQEPTEPKT
KAAAPGVEDEPLLRENPRRFVIFPIEYHDIWQMYKKAEASFWTAEEVDLSKDIQHWESLK
PEERYFISHVLAFFAASDGIVNENLVERFSQEVQITEARCFYGFQIAMENIHSEMYSLLI
DTYIKDPKEREFLFNAIETMPCVKKKADWALRWIGDKEATYGERVVAFAAVEGIFFSGSF
ASIFWLKKRGLMPGLTFSNELISRDEGLHCDFACLMFKHLVHKPSEERVREIIINAVRIE
QEFLTEALPVKLIGMNCTLMKQYIEFVADRLMLELGFSKVFRVENPFDFMENISLEGKTN
FFEKRVGEYQRMGVMSSPTENSFTLDADF
Drugs and Mode of Action
Drug(s) Gemcitabine Drug Info Approved Cancer [468022], [536739]
Hydroxyurea Drug Info Approved Chronic myelogenous leukaemia [537415], [541904]
CO-101 Drug Info Phase 2 Metastatic pancreatic [523237]
Triapine Drug Info Phase 2 Nerve injury [530131]
CALAA-01 Drug Info Phase 1 Solid tumours [522336]
Gemcitabine prodrug Drug Info Phase 1 Cancer [523989], [531557]
LY-2334737 Drug Info Phase 1 Solid tumours [523989]
NKP-46 Drug Info Preclinical Solid tumours [546342]
Gallium maltolate Drug Info Discontinued in Phase 2 Human immunodeficiency virus infection [547230]
MDL 101,731 Drug Info Discontinued in Phase 2 Gastric cancer [545234]
Modulator CALAA-01 Drug Info [1572591]
Gemcitabine Drug Info [556264]
Hydroxyurea Drug Info [556264]
LY-2334737 Drug Info [532325]
MDL 101,731 Drug Info
Triapine Drug Info [530131]
Inhibitor CO-101 Drug Info [528281]
Gemcitabine prodrug Drug Info [528281]
Binder Gallium maltolate Drug Info [528297]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Pyrimidine deoxyribonucleotides biosynthesis from CTP
Pyrimidine deoxyribonucleotides de novo biosynthesis
Guanosine nucleotides de novo biosynthesis
Superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis
Superpathway of purine nucleotide salvage
Purine nucleotides de novo biosynthesis
Adenosine deoxyribonucleotides de novo biosynthesis
Guanosine deoxyribonucleotides de novo biosynthesis
KEGG Pathway Purine metabolism
Pyrimidine metabolism
Glutathione metabolism
Metabolic pathways
p53 signaling pathway
NetPath Pathway EGFR1 Signaling Pathway
PANTHER Pathway p53 pathway
De novo purine biosynthesis
De novo pyrimidine deoxyribonucleotide biosynthesis
Pathway Interaction Database E2F transcription factor network
PathWhiz Pathway Purine Metabolism
Pyrimidine Metabolism
Reactome E2F mediated regulation of DNA replication
G1/S-Specific Transcription
WikiPathways Nucleotide Metabolism
Retinoblastoma (RB) in Cancer
Metabolism of nucleotides
Fluoropyrimidine Activity
References
Ref 468022(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4793).
Ref 522336ClinicalTrials.gov (NCT00689065) Safety Study of CALAA-01 to Treat Solid Tumor Cancers. U.S. National Institutes of Health.
Ref 523237ClinicalTrials.gov (NCT01233375) Study to Evaluate Efficacy of CO-1.01 as Second Line Therapy for Gemcitabine-Refractory Stage IV Pancreatic Adenocarcinoma. U.S. National Institutes of Health.
Ref 523989ClinicalTrials.gov (NCT01648764) A Study of LY2334737 in Participants With Cancer That is Advanced and/or Has Spread. U.S. National Institutes of Health.
Ref 530131PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis. 2009;17(3):611-9.
Ref 531557Phase I study of Oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients with advanced solid tumors. Clin Cancer Res. 2011 Sep 15;17(18):6071-82.
Ref 536739Emerging drugs in cutaneous T cell lymphoma. Expert Opin Emerg Drugs. 2008 Jun;13(2):345-61.
Ref 537415Guidelines of care for the management of psoriasis and psoriatic arthritis Section . Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009 Jun 1.
Ref 541904(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6822).
Ref 545234Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002544)
Ref 546342Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007583)
Ref 547230Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014315)
Ref
Ref 528281Cellular pharmacology of gemcitabine. Ann Oncol. 2006 May;17 Suppl 5:v7-12.
Ref 528297Gallium maltolate is a promising chemotherapeutic agent for the treatment of hepatocellular carcinoma. Anticancer Res. 2006 May-Jun;26(3A):1739-43.
Ref 530131PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis. 2009;17(3):611-9.
Ref 532325Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Jun;71(6):1645-55.
Ref 549988Phase I and pharmacokinetic study of the oral tris-(8-quinolinolato)gallium(III) complex (FFC11, KP46) in patients with solid tumors - a study of the CESAR Central European Society for Anticancer Drug Research - EWIV. J Clin Oncol (Meeting Abstracts) June 2005 vol. 23 no. 16_suppl 3205.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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