Clinical data | |
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Trade names | Hexalen |
Other names | 2,4,6-Tris(dimethylamino)-1,3,5-triazine |
AHFS/ Drugs.com | Monograph |
MedlinePlus | a601200 |
License data |
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Pregnancy category |
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Routes of administration | Oral ( capsules) |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Protein binding | 94% |
Metabolism | Extensive liver |
Metabolites | Pentamethylmelamine, tetramethylmelamine |
Elimination half-life | 4.7–10.2 hours |
Identifiers | |
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CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.010.391 |
Chemical and physical data | |
Formula | C9H18N6 |
Molar mass | 210.285 g·mol−1 |
3D model ( JSmol) | |
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(verify) |
Altretamine (trade name Hexalen), also called hexamethylmelamine, is an antineoplastic agent. It was approved by the U.S. FDA in 1990.
It is indicated for use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with cisplatin and/or alkylating agent-based combination. [1]
It is not considered a first-line treatment, [2] but it can be useful as salvage therapy. [3] It also has the advantage of being less toxic than other drugs used for treating refractory ovarian cancer. [4]
The precise mechanism by which altretamine exerts its anti-cancer effect is unknown but it is classified by MeSH as an alkylating antineoplastic agent. [5]
This unique structure is believed to damage tumor cells through the production of the weakly alkylating species formaldehyde, a product of CYP450-mediated N-demethylation. Administered orally, altretamine is extensively metabolized on first pass, producing primarily mono- and didemethylated metabolites. Additional demethylation reactions occur in tumor cells, releasing formaldehyde in situ before the drug is excreted in the urine. The carbinolamine (methylol) intermediates of CYP450-mediated metabolism also can generate electrophilic iminium species that are capable of reacting covalently with DNA guanine and cytosine residues as well as protein. Iminium-mediated DNA cross-linking and DNA-protein interstrand cross-linking, mediated through both the iminium intermediate and formaldehyde, have been demonstrated, although the significance of DNA cross-linking on altretamine antitumor activity is uncertain. [6]
Side effects include nausea, vomiting, anemia and peripheral sensory neuropathy. [7]
Combination with pyridoxine (vitamin B6) decreases neurotoxicity but has been found to reduce the effectiveness of an altretamine/ cisplatin regime. [8] MAO inhibitor can cause severe orthostatic hypotension when combined with altretamine; and cimetidine can increase its elimination half-life and toxicity. [7]
Clinical data | |
---|---|
Trade names | Hexalen |
Other names | 2,4,6-Tris(dimethylamino)-1,3,5-triazine |
AHFS/ Drugs.com | Monograph |
MedlinePlus | a601200 |
License data |
|
Pregnancy category |
|
Routes of administration | Oral ( capsules) |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Protein binding | 94% |
Metabolism | Extensive liver |
Metabolites | Pentamethylmelamine, tetramethylmelamine |
Elimination half-life | 4.7–10.2 hours |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard ( EPA) | |
ECHA InfoCard | 100.010.391 |
Chemical and physical data | |
Formula | C9H18N6 |
Molar mass | 210.285 g·mol−1 |
3D model ( JSmol) | |
| |
| |
(verify) |
Altretamine (trade name Hexalen), also called hexamethylmelamine, is an antineoplastic agent. It was approved by the U.S. FDA in 1990.
It is indicated for use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with cisplatin and/or alkylating agent-based combination. [1]
It is not considered a first-line treatment, [2] but it can be useful as salvage therapy. [3] It also has the advantage of being less toxic than other drugs used for treating refractory ovarian cancer. [4]
The precise mechanism by which altretamine exerts its anti-cancer effect is unknown but it is classified by MeSH as an alkylating antineoplastic agent. [5]
This unique structure is believed to damage tumor cells through the production of the weakly alkylating species formaldehyde, a product of CYP450-mediated N-demethylation. Administered orally, altretamine is extensively metabolized on first pass, producing primarily mono- and didemethylated metabolites. Additional demethylation reactions occur in tumor cells, releasing formaldehyde in situ before the drug is excreted in the urine. The carbinolamine (methylol) intermediates of CYP450-mediated metabolism also can generate electrophilic iminium species that are capable of reacting covalently with DNA guanine and cytosine residues as well as protein. Iminium-mediated DNA cross-linking and DNA-protein interstrand cross-linking, mediated through both the iminium intermediate and formaldehyde, have been demonstrated, although the significance of DNA cross-linking on altretamine antitumor activity is uncertain. [6]
Side effects include nausea, vomiting, anemia and peripheral sensory neuropathy. [7]
Combination with pyridoxine (vitamin B6) decreases neurotoxicity but has been found to reduce the effectiveness of an altretamine/ cisplatin regime. [8] MAO inhibitor can cause severe orthostatic hypotension when combined with altretamine; and cimetidine can increase its elimination half-life and toxicity. [7]