Details of the Drug

General Information of Drug (ID: DMKLAYG)

Drug Name

Altretamine

Synonyms

Altretamina; Altretaminum; HEXAMETHYLMELAMINE; HMM; HTM; HXM; Hemel; Hexalen; Hexastat; Hexinawas; Altretamine Bellon Brand; Altretamine Chiesi Brand; Altretamine Wassermann Brand; Bellon Brand of Altretamine; Chiesi Brand of Altretamine; MGI Pharma Brand of Altretamine; Rhone Poulenc Rorer Brand of Altretamine; Wassermann Brand of Altretamine; A 8723; ENT 50852; NC 195; Altretamina [INN-Spanish]; Altretaminum [INN-Latin]; Hexalen (TN); Hexalen, Altretamine; KB-913; Rhone-Poulenc Rorer Brand of Altretamine; Altretamine (USP/INN); Altretamine [USAN:INN:BAN]; No-s-triazine; N,N,N',N',N'',N''-hexamethyl-1,3,5-triazine-2,4,6-triamine; N~2~,N~2~,N~4~,N~4~,N~6~,N~6~-Hexamethyl-1,3,5-triazine-2,4,6-triamine; 2,4, 6-Tris(dimethylamino)-1,3,5-triazine; 2,4,6-Tris(dimethylami; 2,4,6-Tris(dimethylamino)-1,3,5-triazine; 2,4,6-Tris(dimethylamino-s-triazine; 2-N,2-N,4-N,4-N,6-N,6-N-hexamethyl-1,3,5-triazine-2,4,6-triamine

Indication

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Approved	[1], [2]

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

210.28

Topological Polar Surface Area (xlogp)

2.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Elimination: 0.5% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 4.7 - 10.2 hours [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 25.72711 micromolar/kg/day [5]

Chemical Identifiers

Formula: C9H18N6
IUPAC Name: 2-N,2-N,4-N,4-N,6-N,6-N-hexamethyl-1,3,5-triazine-2,4,6-triamine
Canonical SMILES: CN(C)C1=NC(=NC(=N1)N(C)C)N(C)C
InChI: InChI=1S/C9H18N6/c1-13(2)7-10-8(14(3)4)12-9(11-7)15(5)6/h1-6H3
InChIKey: UUVWYPNAQBNQJQ-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 2123
ChEBI ID: CHEBI:24564
CAS Number: 645-05-6
DrugBank ID: DB00488
TTD ID: D02LPF
ACDINA ID: D00025

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[6]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Altretamine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylphenobarbital	DMDSWAG	Moderate	Increased metabolism of Altretamine caused by Methylphenobarbital mediated induction of CYP450 enzyme.	Anxiety disorder [6B00-6B0Z]	[17]
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Altretamine and Roflumilast.	Asthma [CA23]	[18]
Desipramine	DMT2FDC	Moderate	Additive hypotensive effects by the combination of Altretamine and Desipramine.	Attention deficit hyperactivity disorder [6A05]	[19]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Ciprofloxacin XR	DM2NLS9	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Ciprofloxacin XR.	Bacterial infection [1A00-1C4Z]	[20]
Trovafloxacin	DM6AN32	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Trovafloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Norfloxacin	DMIZ6W2	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Norfloxacin.	Bacterial infection [1A00-1C4Z]	[20]
ABT-492	DMJFD2I	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[20]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Lomefloxacin	DMVRH9C	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Lomefloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Nortriptyline	DM4KDYJ	Moderate	Additive hypotensive effects by the combination of Altretamine and Nortriptyline.	Depression [6A70-6A7Z]	[19]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Altretamine and Isocarboxazid.	Depression [6A70-6A7Z]	[19]
Tranylcypromine	DMGB5RE	Moderate	Additive hypotensive effects by the combination of Altretamine and Tranylcypromine.	Depression [6A70-6A7Z]	[19]
Phenelzine	DMHIDUE	Moderate	Additive hypotensive effects by the combination of Altretamine and Phenelzine.	Depression [6A70-6A7Z]	[19]
Clomipramine	DMINRKW	Moderate	Additive hypotensive effects by the combination of Altretamine and Clomipramine.	Depression [6A70-6A7Z]	[19]
Amoxapine	DMKITQE	Moderate	Additive hypotensive effects by the combination of Altretamine and Amoxapine.	Depression [6A70-6A7Z]	[19]
Doxepin	DMPI98T	Moderate	Additive hypotensive effects by the combination of Altretamine and Doxepin.	Depression [6A70-6A7Z]	[19]
Primidone	DM0WX6I	Moderate	Increased metabolism of Altretamine caused by Primidone mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Altretamine caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Cimetidine	DMH61ZB	Moderate	Decreased metabolism of Altretamine caused by Cimetidine mediated inhibition of CYP450 enzyme.	Gastro-oesophageal reflux disease [DA22]	[21]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Altretamine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[22]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Altretamine caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[17]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Altretamine and Denosumab.	Low bone mass disorder [FB83]	[23]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Altretamine and Thalidomide.	Multiple myeloma [2A83]	[24]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Altretamine and Tecfidera.	Multiple sclerosis [8A40]	[25]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Altretamine and Siponimod.	Multiple sclerosis [8A40]	[26]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Altretamine and Fingolimod.	Multiple sclerosis [8A40]	[27]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Altretamine and Ocrelizumab.	Multiple sclerosis [8A40]	[28]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Altretamine and Ozanimod.	Multiple sclerosis [8A40]	[18]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Altretamine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[29]
Gatifloxacin	DMSL679	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[20]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Altretamine and Canakinumab.	Rheumatoid arthritis [FA20]	[30]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Altretamine and Rilonacept.	Rheumatoid arthritis [FA20]	[30]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Altretamine and Golimumab.	Rheumatoid arthritis [FA20]	[31]
Leflunomide	DMR8ONJ	Major	Additive immunosuppressive effects by the combination of Altretamine and Leflunomide.	Rheumatoid arthritis [FA20]	[22]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Altretamine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[32]
Azathioprine	DMMZSXQ	Moderate	Additive immunosuppressive effects by the combination of Altretamine and Azathioprine.	Transplant rejection [NE84]	[26]
Cinoxacin	DM4EWNS	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Cinoxacin.	Urinary tract infection [GC08]	[20]
Nalidixic acid	DMRM0JV	Minor	Decreased absorption of Altretamine due to intestinal mucosa variation caused by Nalidixic acid.	Urinary tract infection [GC08]	[20]
Ganciclovir	DM1MBYQ	Moderate	Increased risk of nephrotoxicity by the combination of Altretamine and Ganciclovir.	Virus infection [1A24-1D9Z]	[26]
Valganciclovir	DMS2IUH	Moderate	Increased risk of nephrotoxicity by the combination of Altretamine and Valganciclovir.	Virus infection [1A24-1D9Z]	[26]
-----------


⏷ Show the Full List of 43 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Calcium stearate	E00244	15324	lubricant
--------------------

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Altretamine 50 mg capsule	50 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7112).
2	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019926.
3	BDDCS applied to over 900 drugs
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agen... Cancer Chemother Pharmacol. 2008 Dec;63(1):19-26.
7	Cisplatin and DNA repair in cancer chemotherapy.Trends Biochem Sci.1995 Oct;20(10):435-9.
8	Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
9	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.
10	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.
11	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.
12	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.
13	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.
14	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.
15	Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
16	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.
17	Paolini A, D'Incalci M "Effect of phenobarbital pretreatment on the metabolism and antitumor activity of hexamethylmelamine." Cancer Treat Rep 70 (1986): 513-6. [PMID: 3084083]
18	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19	Bruckner HW, Schleifer SJ "Orthostatic hypotension as a complication of hexamethylmelamine antidepressant interaction." Cancer Treat Rep 67 (1983): 516. [PMID: 6406063]
20	Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
21	Hande K, Combs G, Swingle R, Combs GL, Anthony L "Effect of cimetidine and ranitidine on the metabolism and toxicity of hexamethylmelamine." Cancer Treat Rep 70 (1986): 1443-5. [PMID: 3098418]
22	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
23	Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
24	Figg WD, Arlen P, Gulley J, et al. "A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer." Semin Oncol 28(4 Suppl 15) (2001): 62-6. [PMID: 11685731]
25	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
26	Cerner Multum, Inc. "Australian Product Information.".
27	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
28	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
29	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
30	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
31	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
32	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]