Identification
NameAltretamine
Accession NumberDB00488  (APRD00652)
TypeSmall Molecule
GroupsApproved
Description

An alkylating agent proposed as an antineoplastic. It also acts as a chemosterilant for male houseflies and other insects. [PubChem]

Structure
Thumb
Synonyms
2,4,6-Tris(dimethylamino)-1,3,5-triazine
2,4,6-Tris(dimethylamino)-S-triazine
Altretamin
Altretamina
Altrétamine
Altretaminum
Hexalen
Hexamethylmelamine
Hexastat
HMM
External IDs NSC 13875 / NSC-13875 / RB 1515
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HexalenCapsule50 mg/1OralEisai Limited1990-12-26Not applicableUs
HexalenCapsule50 mgOralEisai Limited1995-12-312013-09-09Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
HexastatProStrakan
Brand mixturesNot Available
Categories
UNIIQ8BIH59O7H
CAS number645-05-6
WeightAverage: 210.2794
Monoisotopic: 210.159294606
Chemical FormulaC9H18N6
InChI KeyUUVWYPNAQBNQJQ-UHFFFAOYSA-N
InChI
InChI=1S/C9H18N6/c1-13(2)7-10-8(14(3)4)12-9(11-7)15(5)6/h1-6H3
IUPAC Name
N2,N2,N4,N4,N6,N6-hexamethyl-1,3,5-triazine-2,4,6-triamine
SMILES
CN(C)C1=NC(=NC(=N1)N(C)C)N(C)C
Pharmacology
Indication

For use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with a cisplatin and/or alkylating agent-based combination.

Structured Indications
Pharmacodynamics

Altretamine is a novel antineoplastic agent. The precise mechanism by which altretamine exerts its cytotoxic effect is unknown, although a number of theoretical possibilities have been studied. Structurally, altretamine resembles the alkylating agent triethylenemelamine, yet in vitro tests for alkylating activity of altretamine and its metabolitics have been negative. Altretamine has been demonstrated to be efficacious for certain ovarian tumors resistant to classical alkylating agents. Metabolism of altretamine is a requirement of cytotoxicity. Synthetic monohydroxymethylmelamines, and products of altretamine metabolism, in vitro and in vivo, can form covalent adducts with tissue macromolecules including DNA, but the relevance of these reactions to antitumor activity is unknown.

Mechanism of action

The precise mechanism by which altretamine exerts its cytotoxic effect is unknown although it is classified as an alkylating anti-neoplastic agent. Through this mechanism, the drug is metabolized into alkylating agents by N-demethylation. These alkylating species consequently damage tumor cells.

TargetKindPharmacological actionActionsOrganismUniProt ID
DNANucleotideyes
other/unknown
Humannot applicabledetails
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding

94%

MetabolismNot Available
Route of elimination

Human urinary metabolites were Ndemethylated homologues of altretamine with <1% unmetabolized altretamine excreted at 24 hours.

Half life

4.7-10.2 hours

ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineAltretamine may increase the orthostatic hypotensive activities of 7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE.Experimental
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Altretamine.Approved
AmineptineAltretamine may increase the orthostatic hypotensive activities of Amineptine.Illicit, Withdrawn
AmitriptylineAltretamine may increase the orthostatic hypotensive activities of Amitriptyline.Approved
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Altretamine.Investigational
BenmoxinAltretamine may increase the orthostatic hypotensive activities of Benmoxin.Withdrawn
BevacizumabBevacizumab may increase the cardiotoxic activities of Altretamine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Altretamine.Approved
CaroxazoneAltretamine may increase the orthostatic hypotensive activities of Caroxazone.Withdrawn
ClomipramineAltretamine may increase the orthostatic hypotensive activities of Clomipramine.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Altretamine is combined with Clozapine.Approved
CyclobenzaprineAltretamine may increase the orthostatic hypotensive activities of Cyclobenzaprine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Altretamine.Approved, Investigational
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Altretamine.Approved
DesipramineAltretamine may increase the orthostatic hypotensive activities of Desipramine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Altretamine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Altretamine.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Altretamine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Altretamine.Approved, Investigational
DosulepinAltretamine may increase the orthostatic hypotensive activities of Dosulepin.Approved
DoxepinAltretamine may increase the orthostatic hypotensive activities of Doxepin.Approved
EsmirtazapineAltretamine may increase the orthostatic hypotensive activities of Esmirtazapine.Investigational
FingolimodAltretamine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FurazolidoneAltretamine may increase the orthostatic hypotensive activities of Furazolidone.Approved, Vet Approved
G17DTThe risk or severity of adverse effects can be increased when Altretamine is combined with G17DT.Investigational
HydracarbazineAltretamine may increase the orthostatic hypotensive activities of Hydracarbazine.Experimental
ImipramineAltretamine may increase the orthostatic hypotensive activities of Imipramine.Approved
INGN 201The risk or severity of adverse effects can be increased when Altretamine is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Altretamine is combined with INGN 225.Investigational
IproclozideAltretamine may increase the orthostatic hypotensive activities of Iproclozide.Withdrawn
IproniazidAltretamine may increase the orthostatic hypotensive activities of Iproniazid.Withdrawn
IsocarboxazidAltretamine may increase the orthostatic hypotensive activities of Isocarboxazid.Approved
LeflunomideThe risk or severity of adverse effects can be increased when Altretamine is combined with Leflunomide.Approved, Investigational
MebanazineAltretamine may increase the orthostatic hypotensive activities of Mebanazine.Withdrawn
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Altretamine.Withdrawn
Methylene blueAltretamine may increase the orthostatic hypotensive activities of Methylene blue.Investigational
MinaprineAltretamine may increase the orthostatic hypotensive activities of Minaprine.Approved
MirtazapineAltretamine may increase the orthostatic hypotensive activities of Mirtazapine.Approved
MoclobemideAltretamine may increase the orthostatic hypotensive activities of Moclobemide.Approved
NatalizumabThe risk or severity of adverse effects can be increased when Altretamine is combined with Natalizumab.Approved, Investigational
NialamideAltretamine may increase the orthostatic hypotensive activities of Nialamide.Withdrawn
NortriptylineAltretamine may increase the orthostatic hypotensive activities of Nortriptyline.Approved
OctamoxinAltretamine may increase the orthostatic hypotensive activities of Octamoxin.Withdrawn
OleandrinAnvirzel may decrease the cardiotoxic activities of Altretamine.Experimental
OpipramolAltretamine may increase the orthostatic hypotensive activities of Opipramol.Investigational
OuabainOuabain may decrease the cardiotoxic activities of Altretamine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Altretamine.Approved, Vet Approved
PargylineAltretamine may increase the orthostatic hypotensive activities of Pargyline.Approved
PhenelzineAltretamine may increase the orthostatic hypotensive activities of Phenelzine.Approved
PheniprazineAltretamine may increase the orthostatic hypotensive activities of Pheniprazine.Withdrawn
PhenoxypropazineAltretamine may increase the orthostatic hypotensive activities of Phenoxypropazine.Withdrawn
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Altretamine.Approved, Investigational
PirlindoleAltretamine may increase the orthostatic hypotensive activities of Pirlindole.Approved
PivhydrazineAltretamine may increase the orthostatic hypotensive activities of Pivhydrazine.Withdrawn
ProtriptylineAltretamine may increase the orthostatic hypotensive activities of Protriptyline.Approved
PyridoxineThe therapeutic efficacy of Altretamine can be decreased when used in combination with Pyridoxine.Approved, Nutraceutical, Vet Approved
RasagilineAltretamine may increase the orthostatic hypotensive activities of Rasagiline.Approved
RindopepimutThe risk or severity of adverse effects can be increased when Altretamine is combined with CDX-110.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Altretamine.Approved
SafrazineAltretamine may increase the orthostatic hypotensive activities of Safrazine.Withdrawn
SelegilineAltretamine may increase the orthostatic hypotensive activities of Selegiline.Approved, Investigational, Vet Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Altretamine.Approved
SRP 299The risk or severity of adverse effects can be increased when Altretamine is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Altretamine.Approved, Investigational
TianeptineAltretamine may increase the orthostatic hypotensive activities of Tianeptine.Approved
TofacitinibAltretamine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
ToloxatoneAltretamine may increase the orthostatic hypotensive activities of Toloxatone.Approved
Trans-2-PhenylcyclopropylamineAltretamine may increase the orthostatic hypotensive activities of Trans-2-Phenylcyclopropylamine.Experimental
TranylcypromineAltretamine may increase the orthostatic hypotensive activities of Tranylcypromine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Altretamine.Approved, Investigational
TrimipramineAltretamine may increase the orthostatic hypotensive activities of Trimipramine.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Keldsen N, Havsteen H, Vergote I, Bertelsen K, Jakobsen A: Altretamine (hexamethylmelamine) in the treatment of platinum-resistant ovarian cancer: a phase II study. Gynecol Oncol. 2003 Feb;88(2):118-22. [PubMed:12586589 ]
  2. Chan JK, Loizzi V, Manetta A, Berman ML: Oral altretamine used as salvage therapy in recurrent ovarian cancer. Gynecol Oncol. 2004 Jan;92(1):368-71. [PubMed:14751188 ]
  3. Malik IA: Altretamine is an effective palliative therapy of patients with recurrent epithelial ovarian cancer. Jpn J Clin Oncol. 2001 Feb;31(2):69-73. [PubMed:11302345 ]
  4. Damia G, D'Incalci M: Clinical pharmacokinetics of altretamine. Clin Pharmacokinet. 1995 Jun;28(6):439-48. [PubMed:7656502 ]
External Links
ATC CodesL01XX03 — Altretamine
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMalignant Lymphomas / Sarcomas1
Pharmacoeconomics
Manufacturers
  • Eisai inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral50 mg/1
CapsuleOral50 mg
Prices
Unit descriptionCostUnit
Hexalen 50 mg capsule12.03USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)168von Brachel, H. and Kindler, H.; U.S. Patent 3,424,752; January 28, 1969; assigned to Casella Farbwerke Mainkur AG
water solubility91 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.73HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility3.1 mg/mLALOGPS
logP2.43ALOGPS
logP2.22ChemAxon
logS-1.8ALOGPS
pKa (Strongest Basic)7.75ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area48.39 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity65.65 m3·mol-1ChemAxon
Polarizability23.7 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9817
Blood Brain Barrier+0.8794
Caco-2 permeable+0.7168
P-glycoprotein substrateNon-substrate0.7414
P-glycoprotein inhibitor INon-inhibitor0.9531
P-glycoprotein inhibitor IINon-inhibitor0.9797
Renal organic cation transporterNon-inhibitor0.7702
CYP450 2C9 substrateNon-substrate0.8369
CYP450 2D6 substrateNon-substrate0.7122
CYP450 3A4 substrateNon-substrate0.5779
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8821
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8293
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8823
BiodegradationNot ready biodegradable0.9793
Rat acute toxicity2.7475 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8907
hERG inhibition (predictor II)Non-inhibitor0.8735
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Download (9.6 KB)
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-3490000000-4af5631898604d2cec10View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03dj-9781100000-4553bbbe9a30a0391bb4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as dialkylarylamines. These are aliphatic aromatic amines in which the amino group is linked to two aliphatic chains and one aromatic group.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic nitrogen compounds
Sub ClassOrganonitrogen compounds
Direct ParentDialkylarylamines
Alternative ParentsN-aliphatic s-triazines / 1,3,5-triazines / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
SubstituentsDialkylarylamine / N-aliphatic s-triazine / Aminotriazine / Amino-1,3,5-triazine / 1,3,5-triazine / Triazine / Heteroaromatic compound / Azacycle / Organoheterocyclic compound / Organopnictogen compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptorstriamino-1,3,5-triazine (CHEBI:24564 )

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
other/unknown
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Damia G, D'Incalci M: Clinical pharmacokinetics of altretamine. Clin Pharmacokinet. 1995 Jun;28(6):439-48. [PubMed:7656502 ]
Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:49