Altretamine

Identification

Name
Altretamine
Accession Number
DB00488  (APRD00652)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • 2,4,6-tris(dimethylamino)-1,3,5-triazine
  • 2,4,6-tris(dimethylamino)-s-triazine
  • Altretamin
  • Altretamina
  • Altrétamine
  • Altretaminum
  • Hexamethylmelamine
  • HMM
External IDs
NSC 13875 / NSC-13875 / RB 1515
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HexalenCapsule50 mg/1OralEisai Limited1990-12-26Not applicableUs
HexalenCapsule50 mgOralEisai Limited1995-12-312013-09-09Canada
International/Other Brands
Hexalen / Hexastat (ProStrakan)
Categories
UNII
Q8BIH59O7H
CAS number
645-05-6
Weight
Average: 210.2794
Monoisotopic: 210.159294606
Chemical Formula
C9H18N6
InChI Key
UUVWYPNAQBNQJQ-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.

Associated Conditions
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.

TargetActionsOrganism
ADNA
other/unknown
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

94%

Metabolism
Not 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

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not 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
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Altretamine.Experimental
AmineptineAltretamine may increase the orthostatic hypotensive activities of Amineptine.Illicit, Withdrawn
AmitriptylineAltretamine may increase the orthostatic hypotensive activities of Amitriptyline.Approved
AmitriptylinoxideAltretamine may increase the orthostatic hypotensive activities of Amitriptylinoxide.Approved, Investigational
AmoxapineAltretamine may increase the orthostatic hypotensive activities of Amoxapine.Approved
AmphetamineAltretamine may increase the orthostatic hypotensive activities of Amphetamine.Approved, Illicit, Investigational
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Altretamine.Approved, Investigational, Withdrawn
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Altretamine is combined with Anthrax immune globulin human.Approved
Bacillus calmette-guerin substrain connaught live antigenThe risk or severity of adverse effects can be increased when Altretamine is combined with Bacillus calmette-guerin substrain connaught live antigen.Approved, Investigational
Bacillus calmette-guerin substrain tice live antigenThe risk or severity of adverse effects can be increased when Altretamine is combined with Bacillus calmette-guerin substrain tice live antigen.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine 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
BrofaromineAltretamine may increase the orthostatic hypotensive activities of Brofaromine.Experimental
ButriptylineAltretamine may increase the orthostatic hypotensive activities of Butriptyline.Approved
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, Investigational, Vet Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Altretamine is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated).Approved
ClozapineThe risk or severity of adverse effects can be increased when Altretamine is combined with Clozapine.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Altretamine is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated).Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Altretamine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Altretamine.Experimental
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, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Altretamine.Approved
DibenzepinAltretamine may increase the orthostatic hypotensive activities of Dibenzepin.Experimental
DigitoxinDigitoxin may decrease the cardiotoxic activities of Altretamine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Altretamine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Altretamine.Approved
DimetacrineAltretamine may increase the orthostatic hypotensive activities of Dimetacrine.Approved, Withdrawn
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, Investigational
FingolimodAltretamine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FurazolidoneAltretamine may increase the orthostatic hypotensive activities of Furazolidone.Approved, Investigational, Vet Approved
G17DTThe risk or severity of adverse effects can be increased when Altretamine is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Altretamine is combined with GI-5005.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Altretamine.Experimental
HarmalineAltretamine may increase the orthostatic hypotensive activities of Harmaline.Experimental
Hepatitis A VaccineThe risk or severity of adverse effects can be increased when Altretamine is combined with Hepatitis A Vaccine.Approved
Hepatitis B Vaccine (Recombinant)The risk or severity of adverse effects can be increased when Altretamine is combined with Hepatitis B Vaccine (Recombinant).Approved, Withdrawn
Human rabies virus immune globulinThe risk or severity of adverse effects can be increased when Altretamine is combined with Human rabies virus immune globulin.Approved
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
IprindoleAltretamine may increase the orthostatic hypotensive activities of Iprindole.Experimental
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
Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Altretamine is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated).Approved
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Altretamine.Experimental
LeflunomideThe risk or severity of adverse effects can be increased when Altretamine is combined with Leflunomide.Approved, Investigational
LipegfilgrastimAltretamine may increase the myelosuppressive activities of Lipegfilgrastim.Approved, Investigational
LofepramineAltretamine may increase the orthostatic hypotensive activities of Lofepramine.Experimental
MebanazineAltretamine may increase the orthostatic hypotensive activities of Mebanazine.Withdrawn
MelitracenAltretamine may increase the orthostatic hypotensive activities of Melitracen.Experimental, Investigational
MetamizoleThe risk or severity of myelosuppression can be increased when Metamizole is combined with Altretamine.Approved, Investigational, Withdrawn
Methylene blueAltretamine may increase the orthostatic hypotensive activities of Methylene blue.Approved, Investigational
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Altretamine.Experimental
MinaprineAltretamine may increase the orthostatic hypotensive activities of Minaprine.Approved
MoclobemideAltretamine may increase the orthostatic hypotensive activities of Moclobemide.Approved, Investigational
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
OcrelizumabOcrelizumab may increase the immunosuppressive activities of Altretamine.Approved, Investigational
OctamoxinAltretamine may increase the orthostatic hypotensive activities of Octamoxin.Withdrawn
OleandrinOleandrin may decrease the cardiotoxic activities of Altretamine.Experimental, Investigational
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
PeruvosidePeruvoside may decrease the cardiotoxic activities of Altretamine.Experimental
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
ProcaineAltretamine may increase the orthostatic hypotensive activities of Procaine.Approved, Investigational, Vet Approved
ProcarbazineAltretamine may increase the orthostatic hypotensive activities of Procarbazine.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Altretamine.Experimental
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, Investigational, Nutraceutical, Vet Approved
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Altretamine is combined with Rabies virus inactivated antigen, A.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Altretamine.Approved, Investigational
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 Rindopepimut.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Altretamine.Approved
Rotavirus VaccineThe risk or severity of adverse effects can be increased when Altretamine is combined with Rotavirus Vaccine.Approved
Rubella virus vaccineThe risk or severity of adverse effects can be increased when Altretamine is combined with Rubella virus vaccine.Approved, Investigational
SafrazineAltretamine may increase the orthostatic hypotensive activities of Safrazine.Withdrawn
Salmonella typhi ty2 vi polysaccharide antigenThe risk or severity of adverse effects can be increased when Altretamine is combined with Salmonella typhi ty2 vi polysaccharide antigen.Approved
Salmonella typhi ty21a live antigenThe risk or severity of adverse effects can be increased when Altretamine is combined with Salmonella typhi ty21a live antigen.Approved
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, Investigational
SRP 299The risk or severity of adverse effects can be increased when Altretamine is combined with SRP 299.Investigational
TacrolimusTacrolimus may increase the immunosuppressive activities of Altretamine.Approved, Investigational
TecemotideThe risk or severity of adverse effects can be increased when Altretamine is combined with Tecemotide.Investigational
TG4010The risk or severity of adverse effects can be increased when Altretamine is combined with TG4010.Investigational
TianeptineAltretamine may increase the orthostatic hypotensive activities of Tianeptine.Approved, Investigational
TofacitinibAltretamine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
ToloxatoneAltretamine may increase the orthostatic hypotensive activities of Toloxatone.Approved
TranylcypromineAltretamine may increase the orthostatic hypotensive activities of Tranylcypromine.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Altretamine.Approved, Investigational
TrimipramineAltretamine may increase the orthostatic hypotensive activities of Trimipramine.Approved
Typhoid VaccineThe risk or severity of adverse effects can be increased when Altretamine is combined with Typhoid Vaccine.Approved
Varicella Zoster Vaccine (Live/Attenuated)The risk or severity of adverse effects can be increased when Altretamine is combined with Varicella Zoster Vaccine (Live/Attenuated).Approved
Yellow Fever VaccineThe risk or severity of adverse effects can be increased when Altretamine is combined with Yellow Fever Vaccine.Approved, Investigational
Food Interactions
Not Available

References

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
Human Metabolome Database
HMDB0014631
PubChem Compound
2123
PubChem Substance
46505760
ChemSpider
2038
BindingDB
37631
ChEBI
24564
ChEMBL
CHEMBL1455
Therapeutic Targets Database
DAP000989
PharmGKB
PA164743136
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Altretamine
ATC Codes
L01XX03 — Altretamine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMalignant Lymphomas / Sarcomas1

Pharmacoeconomics

Manufacturers
  • Eisai inc
Packagers
  • AAIPharma Inc.
  • Eisai Inc.
  • Excella GmbH
  • MGI Pharma
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.
Patents
Not Available

Properties

State
Solid
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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-3490000000-4af5631898604d2cec10
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03dj-9781100000-4553bbbe9a30a0391bb4

Taxonomy

Description
This compound belongs to the class of organic compounds known as dialkylarylamines. These are aliphatic aromatic amines in which the amino group is linked to two aliphatic chains and one aromatic group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Dialkylarylamines
Alternative Parents
N-aliphatic s-triazines / 1,3,5-triazines / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Dialkylarylamine / N-aliphatic s-triazine / Aminotriazine / Amino-1,3,5-triazine / 1,3,5-triazine / Triazine / Heteroaromatic compound / Azacycle / Organoheterocyclic compound / Organopnictogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
triamino-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 02, 2018 17:19