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

General Information of Drug (ID: DMFKOR9)

• Drug Name: Pafuramidine Drug Info
• Synonyms: Pafuramidine maleate; DB-289; DB-290; DB-75 prodrug, Immtech; Pafuramidine maleate (oral formulation), Strativa

Indication

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 5480200
  CAS Number: CAS 186953-56-0
  TTD Drug ID: DMFKOR9
  INTEDE Drug ID: DR1892

Molecule-Related Drug Atlas

Drug(s) Targeting Human Deoxyribonucleic acid (hDNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[4]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[5]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[6]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[7]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[8]
Carboplatin	DMG281S	Adenocarcinoma	2D40	Approved	[9]
Busulfan	DMXYJ9C	Chronic myelogenous leukaemia	2A20.0	Approved	[10]
Procarbazine	DMIK367	Hodgkin lymphoma	2B30	Approved	[11]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[12]
Dacarbazine	DMNPZL4	Adenocarcinoma	2D40	Approved	[13]

Drug(s) Metabolized By Cytochrome P450 4F2 (CYP4F2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[14]
Fingolimod	DM5JVAN	Multiple sclerosis	8A40	Approved	[15]
Ebastine	DMH21D9	N. A.	N. A.	Phase 4	[16]
Tocopherol	DMBIJZ6	N. A.	N. A.	Phase 2	[17]
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[18]
Arachidonic Acid	DMUOQZD	Discovery agent	N.A.	Investigative	[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]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 4F2 (CYP4F2) Main DME	DE3GT9C	CP4F2_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT00302341) DB289 Versus TMP-SMX for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP). U.S. National Institutes of Health.
• [2] DNA Minor Groove Induced Dimerization of Heterocyclic Cations: Compound Structure, Binding Affinity and Specificity for a TTAA Site
• [3] Human enteric microsomal CYP4F enzymes O-demethylate the antiparasitic prodrug pafuramidine. Drug Metab Dispos. 2007 Nov;35(11):2067-75.
• [4] Cisplatin and DNA repair in cancer chemotherapy.Trends Biochem Sci.1995 Oct;20(10):435-9.
• [5] Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
• [13] 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.
• [14] Cloning and characterization of CYP4F21: a prostaglandin E2 20-hydroxylase of ram seminal vesicles. Arch Biochem Biophys. 2001 May 1;389(1):123-9.
• [15] CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis. Drug Metab Dispos. 2011 Feb;39(2):191-8.
• [16] cDNA cloning and expression of a novel cytochrome p450 (cyp4f12) from human small intestine. Biochem Biophys Res Commun. 2001 Feb 2;280(4):1135-41.
• [17] Discovery, characterization, and significance of the cytochrome P450 omega-hydroxylase pathway of vitamin E catabolism. Ann N Y Acad Sci. 2004 Dec;1031:13-21.
• [18] Product information - Gilenya.
• [19] Role of cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids. Biochim Biophys Acta. 2011 Jan;1814(1):210-22.