Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMCBV20)

• Drug Name: LY-2334737 Drug Info
• Synonyms: Gem prodrug (cancer), Eli Lilly; Gemcitabine prodrug (cancer), Lilly

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 11646777
  CAS Number: CAS 892128-60-8
  TTD Drug ID: DMCBV20

Molecule-Related Drug Atlas

Drug(s) Targeting Ribonucleoside-diphosphate reductase M2 (RRM2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gemcitabine	DMSE3I7	Anterior urethra cancer		Approved	[3]
Hydroxyurea	DMOQVU9	Chronic myelogenous leukaemia	2A20.0	Approved	[3]
CO-101	DMH5GQU	Pancreatic cancer	2C10	Phase 2	[4]
Triapine	DM7XZY5	Nerve injury	ND56.4	Phase 2	[5]
CALAA-01	DMT4Z5B	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
Gallium maltolate	DMX0Z51	Human immunodeficiency virus infection	1C62	Discontinued in Phase 2	[7]
MDL 101,731	DMKEYSX	Gastric adenocarcinoma	2B72	Discontinued in Phase 2	[8]
NKP-46	DMK8UD0	Solid tumour/cancer	2A00-2F9Z	Preclinical	[9]

Drug(s) Targeting Human Deoxyribonucleic acid (hDNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[10]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[11]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[12]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[13]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[14]
Carboplatin	DMG281S	Adenocarcinoma	2D40	Approved	[15]
Busulfan	DMXYJ9C	Chronic myelogenous leukaemia	2A20.0	Approved	[16]
Procarbazine	DMIK367	Hodgkin lymphoma	2B30	Approved	[17]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[18]
Dacarbazine	DMNPZL4	Adenocarcinoma	2D40	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[2]
Ribonucleoside-diphosphate reductase M2 (RRM2)	TTBWDI0	RIR2_HUMAN	Modulator	[2]

References

• [1] ClinicalTrials.gov (NCT01648764) A Study of LY2334737 in Participants With Cancer That is Advanced and/or Has Spread. U.S. National Institutes of Health.
• [2] Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Jun;71(6):1645-55.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Cellular pharmacology of gemcitabine. Ann Oncol. 2006 May;17 Suppl 5:v7-12.
• [5] 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.
• [6] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [7] Gallium maltolate is a promising chemotherapeutic agent for the treatment of hepatocellular carcinoma. Anticancer Res. 2006 May-Jun;26(3A):1739-43.
• [8] Tezacitabine Hoechst Marion Roussel.Curr Opin Investig Drugs.2000 Sep;1(1):135-40.
• [9] 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.
• [10] Cisplatin and DNA repair in cancer chemotherapy.Trends Biochem Sci.1995 Oct;20(10):435-9.
• [11] Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
• [12] 31P NMR spectra of ethidium, quinacrine, and daunomycin complexes with poly(adenylic acid).poly(uridylic acid) RNA duplex and calf thymus DNA. Biochemistry. 1989 Apr 4;28(7):2804-12.
• [13] Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35.
• [14] O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts. Int J Cancer. 1998 Sep 11;77(6):919-22.
• [15] Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
• [16] DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect. Cancer Sci. 2004 May;95(5):454-8.
• [17] Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations... DNA Repair (Amst). 2009 Jan 1;8(1):72-86.
• [18] Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
• [19] Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mono... Melanoma Res. 2011 Dec;21(6):502-8.