Altretamine

Identification

Summary

Altretamine is an antineoplastic agent used in palliative treatment of persistent or recurrent ovarian cancer.

Generic Name
Altretamine
DrugBank Accession Number
DB00488
Background

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

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 210.2794
Monoisotopic: 210.159294606
Chemical Formula
C9H18N6
Synonyms
  • 2,4,6-tris(dimethylamino)-1,3,5-triazine
  • 2,4,6-tris(dimethylamino)-s-triazine
  • Altretamin
  • Altretamina
  • Altrétamine
  • Altretamine
  • Altretaminum
  • Hexamethylmelamine
  • HMM
External IDs
  • NSC 13875
  • NSC-13875
  • RB 1515

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.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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
Humans
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

Adverse Effects
Medicalerrors
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Altretamine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Altretamine.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Altretamine.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Altretamine.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Altretamine.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Altretamine.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Altretamine.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Altretamine.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Altretamine.
AllopurinolThe risk or severity of adverse effects can be increased when Allopurinol is combined with Altretamine.
Interactions
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Food Interactions
  • Take after a meal. Take altretamine after meals and at bedtime.

Products

Products
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International/Other Brands
Hexastat (ProStrakan)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HexalenCapsule50 mg/1OralEisai Inc.1990-12-262019-12-31US flag
HexalenCapsule50 mgOralEisai Limited1995-12-312013-09-09Canada flag
HexalenCapsule50 mg/1OralMGI PHARMA, INC.1990-12-262011-12-31US flag

Categories

ATC Codes
L01XX03 — Altretamine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,3,5-triazine / Amino-1,3,5-triazine / Aminotriazine / Aromatic heteromonocyclic compound / Azacycle / Dialkylarylamine / Heteroaromatic compound / Hydrocarbon derivative / N-aliphatic s-triazine / Organoheterocyclic compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
triamino-1,3,5-triazine (CHEBI:24564)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Q8BIH59O7H
CAS number
645-05-6
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

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. [Article]
  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. [Article]
  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. [Article]
  4. Damia G, D'Incalci M: Clinical pharmacokinetics of altretamine. Clin Pharmacokinet. 1995 Jun;28(6):439-48. [Article]
Human Metabolome Database
HMDB0014631
PubChem Compound
2123
PubChem Substance
46505760
ChemSpider
2038
BindingDB
37631
RxNav
5296
ChEBI
24564
ChEMBL
CHEMBL1455
ZINC
ZINC000000000905
Therapeutic Targets Database
DAP000989
PharmGKB
PA164743136
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
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
CapsuleOral
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

Targets

Drugtargets
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Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Other/unknown
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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. [Article]
  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. [Article]
  3. Damia G, D'Incalci M: Clinical pharmacokinetics of altretamine. Clin Pharmacokinet. 1995 Jun;28(6):439-48. [Article]

Drug created on June 13, 2005 13:24 / Updated on March 04, 2021 11:13