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
Structure for Altretamine (DB00488)
- 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.
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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.
Target Actions Organism ADNA other/unknownHumans - 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
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Altretamine is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Altretamine. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Altretamine. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Altretamine. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Altretamine. - Food Interactions
- Take after a meal. Take altretamine after meals and at bedtime.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Hexastat (ProStrakan)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Hexalen Capsule 50 mg/1 Oral MGI PHARMA, INC. 1990-12-26 2011-12-31 US 
Hexalen Capsule 50 mg/1 Oral Eisai Inc. 1990-12-26 2019-12-31 US Hexalen Capsule 50 mg Oral Eisai Limited 1995-12-31 2013-09-09 Canada 
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
- 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]
- 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]
- 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]
- Damia G, D'Incalci M: Clinical pharmacokinetics of altretamine. Clin Pharmacokinet. 1995 Jun;28(6):439-48. [Article]
- External Links
- Human Metabolome Database
- HMDB0014631
- PubChem Compound
- 2123
- PubChem Substance
- 46505760
- ChemSpider
- 2038
- BindingDB
- 37631
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Pharmacoeconomics
- Manufacturers
- Eisai inc
- Packagers
- AAIPharma Inc.
- Eisai Inc.
- Excella GmbH
- MGI Pharma
- Dosage Forms
Form Route Strength Capsule Oral 50 mg/1 Capsule Oral 50 mg Capsule Oral - Prices
Unit description Cost Unit Hexalen 50 mg capsule 12.03USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 168 von Brachel, H. and Kindler, H.; U.S. Patent 3,424,752; January 28, 1969; assigned to Casella Farbwerke Mainkur AG water solubility 91 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 2.73 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 3.1 mg/mL ALOGPS logP 2.43 ALOGPS logP 2.22 Chemaxon logS -1.8 ALOGPS pKa (Strongest Basic) 8.75 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 48.39 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 65.65 m3·mol-1 Chemaxon Polarizability 23.7 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9817 Blood Brain Barrier + 0.8794 Caco-2 permeable + 0.7168 P-glycoprotein substrate Non-substrate 0.7414 P-glycoprotein inhibitor I Non-inhibitor 0.9531 P-glycoprotein inhibitor II Non-inhibitor 0.9797 Renal organic cation transporter Non-inhibitor 0.7702 CYP450 2C9 substrate Non-substrate 0.8369 CYP450 2D6 substrate Non-substrate 0.7122 CYP450 3A4 substrate Non-substrate 0.5779 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8821 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8293 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.8823 Biodegradation Not ready biodegradable 0.9793 Rat acute toxicity 2.7475 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8907 hERG inhibition (predictor II) Non-inhibitor 0.8735
Spectra
- Mass Spec (NIST)
- Download (9.6 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 159.9917382 predictedDarkChem Lite v0.1.0 [M-H]- 160.1390382 predictedDarkChem Lite v0.1.0 [M-H]- 150.45659 predictedDeepCCS 1.0 (2019) [M+H]+ 160.2959382 predictedDarkChem Lite v0.1.0 [M+H]+ 159.8430382 predictedDarkChem Lite v0.1.0 [M+H]+ 152.85213 predictedDeepCCS 1.0 (2019) [M+Na]+ 160.1955382 predictedDarkChem Lite v0.1.0 [M+Na]+ 160.1320382 predictedDarkChem Lite v0.1.0 [M+Na]+ 158.884 predictedDeepCCS 1.0 (2019)
Targets
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Yes
Other/unknown
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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]
- Damia G, D'Incalci M: Clinical pharmacokinetics of altretamine. Clin Pharmacokinet. 1995 Jun;28(6):439-48. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2023 23:43