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

General Information of Drug (ID: DMQR4HA)

• Drug Name: DABIS MALEATE Drug Info
• Synonyms: E-83-041; 1,4-Bis(2-chloroethyl)-1,4-diazoniabicyclo[2.2.1]heptane dimaleate

Indication

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

• Cross-matching ID:
  PubChem CID: 54599345
  CAS Number: CAS 73387-70-9
  TTD Drug ID: DMQR4HA

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	[3]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[4]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[5]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[6]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[7]
Carboplatin	DMG281S	Adenocarcinoma	2D40	Approved	[8]
Busulfan	DMXYJ9C	Chronic myelogenous leukaemia	2A20.0	Approved	[9]
Procarbazine	DMIK367	Hodgkin lymphoma	2B30	Approved	[10]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[11]
Dacarbazine	DMNPZL4	Adenocarcinoma	2D40	Approved	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Binder	[2]

References

• [1] Phase I study of DABIS maleate given once every 3 weeks. Eur J Cancer. 1991;27(12):1635-7.
• [2] DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate)Broggini M1, Hartley JA, Mattes WB, Ponti M, Kohn KW, D'Incalci M.Author information1Laboratory of Cancer Chemotherapy, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.Erratum inBr J Cancer 1990 Jul;62(1):172. AbstractThe DNA damage and the sequence specificity of guanine-N7 alkylation produced by the novel, positively charged, antineoplastic agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) and its uncharged tertiary amine analogue 1,4-bis(2'-chloroethyl)-1,4-diazacyclohexane (Dabis analogue) were investigated in L1210 cells and isolated DNA. Both compounds are cytotoxic in vitro causing an arrest of L1210 cells in G2/M phase of the cell cycle. In isolated DNA, Dabis maleate alkylates guanine at the N7-position with some differences in specificity compared to other alkylating agents (e.g. nitrogen mustard). Significant differences are also evident between Dabis maleate and Dabis analogue, suggesting that Dabis analogue is not the sole alkylating species of Dabis maleate. Using the alkaline elution technique a moderate number of DNA interstrand cross-links were detected in L1210 cells treated with both compounds, which were completely repaired within 24 h. Dabis maleate and Dabis analogue do not cause DNA single strand breaks or DNA protein cross-links at the doses at which DNA interstrand cross-links were detected.PMID: 2393411 [PubMed - indexed for MEDLINE] PMCID: PMC1971404 Free PMC ArticleSharePublication Types, MeSH Terms, SubstancesPublication TypesResearch Support, Non-U.S. Gov'tMeSH TermsAnimalsAntineoplastic Agents/pharmacology*Base SequenceBicycloCompounds/pharmacology*Bicyclo Compounds, Heterocyclic*Bridged Compounds/pharmacology*Cell Survival/drug effectsDNA Damage*DNA, Neoplasm/drug effects*Dose-Response Relationship, DrugHumansInterphase/drug effectsLeukemia L1210/pathologyTumor Cells, Cultured/drug effectsSubstancesAntineoplastic AgentsBicyclo CompoundsBicyclo Compounds, HeterocyclicBridged CompoundsDNA, Neoplasm1,4-bis(2'-chloroethyl)-1,4-diazabicyclo(2.2.1)heptaneLinkOut - more resourcesFull Text SourcesEurope PubMed CentralPubMed CentralPubMed Central CanadaOther Literature SourcesCOS Scholar UniverseAccess more work from the authors - ResearchGateMiscellaneousNCI CPTAC Assay PortalPubMed Commons home Br J Cancer. 1990 Feb;61(2):285-9.
• [3] Cisplatin and DNA repair in cancer chemotherapy.Trends Biochem Sci.1995 Oct;20(10):435-9.
• [4] Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
• [12] 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.