Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTBWDI0)

• DTT Name: Ribonucleoside-diphosphate reductase M2 (RRM2)
• Synonyms: Ribonucleotide reductase small subunit; Ribonucleotide reductase small chain; Ribonucleoside-diphosphate reductase subunit M2; RR2
• Gene Name: RRM2
• DTT Type: Successful target; [1]
• BioChemical Class: CH/CH(2) oxidoreductase
• UniProt ID: RIR2_HUMAN
• TTD ID: T38301
• EC Number: EC 1.17.4.1
• Sequence:
  MLSLRVPLAPITDPQQLQLSPLKGLSLVDKENTPPALSGTRVLASKTARRIFQEPTEPKT
  KAAAPGVEDEPLLRENPRRFVIFPIEYHDIWQMYKKAEASFWTAEEVDLSKDIQHWESLK
  PEERYFISHVLAFFAASDGIVNENLVERFSQEVQITEARCFYGFQIAMENIHSEMYSLLI
  DTYIKDPKEREFLFNAIETMPCVKKKADWALRWIGDKEATYGERVVAFAAVEGIFFSGSF
  ASIFWLKKRGLMPGLTFSNELISRDEGLHCDFACLMFKHLVHKPSEERVREIIINAVRIE
  QEFLTEALPVKLIGMNCTLMKQYIEFVADRLMLELGFSKVFRVENPFDFMENISLEGKTN
  FFEKRVGEYQRMGVMSSPTENSFTLDADF
• Function: Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling. Provides the precursors necessary for DNA synthesis.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  p53 signaling pathway (hsa04115)
• Reactome Pathway:
  G1/S-Specific Transcription (R-HSA-69205)
  E2F mediated regulation of DNA replication (R-HSA-113510)
• BioCyc Pathway: MetaCyc:HS10398-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gemcitabine	DMSE3I7	Anterior urethra cancer		Approved	[1]
Hydroxyurea	DMOQVU9	Chronic myelogenous leukaemia	2A20.0	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CO-101	DMH5GQU	Pancreatic cancer	2C10	Phase 2	[2]
Triapine	DM7XZY5	Nerve injury	ND56.4	Phase 2	[3]
CALAA-01	DMT4Z5B	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
LY-2334737	DMCBV20	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gallium maltolate	DMX0Z51	Human immunodeficiency virus infection	1C62	Discontinued in Phase 2	[6]
MDL 101,731	DMKEYSX	Gastric adenocarcinoma	2B72	Discontinued in Phase 2	[7]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NKP-46	DMK8UD0	Solid tumour/cancer	2A00-2F9Z	Preclinical	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Pancreatic cancer	2C82	Pancreas	1.66E-04	2.66	1.68

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [2] Cellular pharmacology of gemcitabine. Ann Oncol. 2006 May;17 Suppl 5:v7-12.
• [3] PAN-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.
• [4] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [5] Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Jun;71(6):1645-55.
• [6] Gallium maltolate is a promising chemotherapeutic agent for the treatment of hepatocellular carcinoma. Anticancer Res. 2006 May-Jun;26(3A):1739-43.
• [7] Tezacitabine Hoechst Marion Roussel.Curr Opin Investig Drugs.2000 Sep;1(1):135-40.
• [8] Phase 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.