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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 Identifiers
  • NSC 13875
  • RB 1515
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hexalencapsule50 mg/1oralEisai Inc.1990-12-26Not applicableUs
Hexalencapsule50 mgoralEisai Inc1995-12-312013-09-09Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
HexastatProStrakan
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIQ8BIH59O7H
CAS number645-05-6
WeightAverage: 210.2794
Monoisotopic: 210.159294606
Chemical FormulaC9H18N6
InChI KeyInChIKey=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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-aliphatic s-triazines. These are n-aliphatic amine derivatives of 1,3,5-triazines. 1,3,5-triazines are aromatic compounds having three nitrogen ring atoms at the 1-, 3-, and 5- positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassTriazines
Sub ClassAminotriazines
Direct ParentN-aliphatic s-triazines
Alternative Parents
Substituents
  • Dialkylarylamine
  • N-aliphatic s-triazine
  • 1,3,5-triazine
  • Heteroaromatic compound
  • Tertiary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsAltretamine 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 actionThe 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding94%
MetabolismNot Available
Route of eliminationHuman urinary metabolites were Ndemethylated homologues of altretamine with <1% unmetabolized altretamine excreted at 24 hours.
Half life4.7-10.2 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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 point168von 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.6 KB)
Spectra
Spectrum TypeDescriptionSplash Key
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
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
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmitriptylineAltretamine may increase the orthostatic hypotensive activities of Amitriptyline.
AmoxapineAltretamine may increase the orthostatic hypotensive activities of Amoxapine.
ClomipramineAltretamine may increase the orthostatic hypotensive activities of Clomipramine.
ClozapineThe risk or severity of adverse effects can be increased when Altretamine is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Altretamine.
DesipramineAltretamine may increase the orthostatic hypotensive activities of Desipramine.
DoxepinAltretamine may increase the orthostatic hypotensive activities of Doxepin.
ImipramineAltretamine may increase the orthostatic hypotensive activities of Imipramine.
IsocarboxazidAltretamine may increase the orthostatic hypotensive activities of Isocarboxazid.
LeflunomideThe risk or severity of adverse effects can be increased when Altretamine is combined with Leflunomide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Altretamine.
MoclobemideAltretamine may increase the orthostatic hypotensive activities of Moclobemide.
NatalizumabThe risk or severity of adverse effects can be increased when Altretamine is combined with Natalizumab.
NortriptylineAltretamine may increase the orthostatic hypotensive activities of Nortriptyline.
PhenelzineAltretamine may increase the orthostatic hypotensive activities of Phenelzine.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Altretamine.
ProcarbazineAltretamine may increase the orthostatic hypotensive activities of Procarbazine.
ProtriptylineAltretamine may increase the orthostatic hypotensive activities of Protriptyline.
PyridoxineThe therapeutic efficacy of Altretamine can be decreased when used in combination with Pyridoxine.
RasagilineAltretamine may increase the orthostatic hypotensive activities of Rasagiline.
RoflumilastRoflumilast may increase the immunosuppressive activities of Altretamine.
SelegilineAltretamine may increase the orthostatic hypotensive activities of Selegiline.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Altretamine.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Altretamine.
TofacitinibAltretamine may increase the immunosuppressive activities of Tofacitinib.
TranylcypromineAltretamine may increase the orthostatic hypotensive activities of Tranylcypromine.
TrastuzumabTrastuzumab may increase the neutropenic activities of Altretamine.
TrimipramineAltretamine may increase the orthostatic hypotensive activities of Trimipramine.
Food InteractionsNot Available

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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23