General Information of Drug (ID: DMH2EA1)

Drug Name
Laromustine Drug Info
Synonyms Cloretazine; Onrigin; Alkylating agents, Vion; SHP, Vion; Sulfonyl hydrazine prodrugs, Vion; VN-40101M; VNP-40101M; VNP-4090-CE; 90CE
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 3 [1]
Cross-matching ID
PubChem CID
3081349
CAS Number
CAS 173424-77-6
TTD Drug ID
DMH2EA1

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Approved Drug(s)
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]
⏷ Show the Full List of 10 Drug(s)
Drug Name Drug ID Indication ICD 11 Highest Status REF
DTI-015 DMXZRW0 Brain cancer 2A00 Approved [14]
Cyclophosphamide DM4O2Z7 Advanced cancer 2A00-2F9Z Approved [15]
Acocantherin DM7JT24 Atrial fibrillation BC81.3 Approved [16]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [17]
Disulfiram DMCL2OK Alcohol dependence 6C40.2 Approved [18]
Ivermectin DMDBX5F Intestinal strongyloidiasis due to nematode parasite 1F6B Approved [19]
Dexamethasone DMMWZET Acute adrenal insufficiency Approved [20]
Phenytoin DMNOKBV Epilepsy 8A60-8A68 Approved [21]
Dacarbazine DMNPZL4 Adenocarcinoma 2D40 Approved [22]
Topotecan DMP6G8T Central nervous system neoplasm Approved [23]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Gene/Protein Processing [3]

References

1 ClinicalTrials.gov (NCT00112554) Cytarabine With or Without VNP40101M in Treating Patients With Relapsed Acute Myeloid Leukemia. U.S. National Institutes of Health.
2 Phase I study of temozolomide and laromustine (VNP40101M) in patients with relapsed or refractory leukemia. Clin Lymphoma Myeloma Leuk. 2010 Jun;10(3):211-6.
3 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT) by electrophilic species generated by decomposition. Cancer Chemother Pharmacol. 2004 Apr;53(4):279-87. doi: 10.1007/s00280-003-0740-7. Epub 2003 Dec 24.
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 Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.
15 Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
16 Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways. Environ Toxicol. 2019 Dec;34(12):1329-1339. doi: 10.1002/tox.22834. Epub 2019 Aug 21.
17 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
18 Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage. Carcinogenesis. 2014 Mar;35(3):692-702. doi: 10.1093/carcin/bgt366. Epub 2013 Nov 5.
19 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
20 Induction of the DNA repair gene O6-methylguanine-DNA methyltransferase by dexamethasone in glioblastomas. J Neurosurg. 2004 Oct;101(4):659-63. doi: 10.3171/jns.2004.101.4.0659.
21 Phenytoin may increase the efficacy of temozolomide by methylating DNA-repair enzyme, O6-methylguanine-DNA methyltransferase in patients with glioblastoma. Med Hypotheses. 2005;65(4):819-20. doi: 10.1016/j.mehy.2005.04.007.
22 Pharmacokinetic, biochemical and clinical effects of dimethyltriazenoimidazole-4-carboxamide-bischloroethylnitrosourea combination therapy in patients with advanced breast cancer. Int J Cancer. 2003 Feb 20;103(5):686-92. doi: 10.1002/ijc.10849.
23 Transcriptional repression of O6-methylguanine DNA methyltransferase gene rendering cells hypersensitive to N,N'-bis(2-chloroethyl)-N-nitrosurea in camptothecin-resistant cells. Mol Pharmacol. 2008 Aug;74(2):517-26. doi: 10.1124/mol.107.043620. Epub 2008 May 20.