Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/20 03:01:30」(JST)
[Wiki en表示]
Hexamethylmelamine
|
|
| Systematic (IUPAC) name |
|
N2,N2,N4,N4,N6,N6-hexamethyl-1,3,5-triazine-2,4,6-triamine
|
| Clinical data |
| Trade names |
Hexalen |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a601200 |
| Licence data |
US FDA:link |
Pregnancy
category |
- AU: D
- US: D (Evidence of risk)
|
| Legal status |
- AU: S4 (Prescription only)
- CA: ℞-only
- US: ℞-only
|
| Pharmacokinetic data |
| Protein binding |
94% |
| Biological half-life |
4.7-10.2 hours |
| Identifiers |
| CAS Number |
645-05-6 Y |
| ATC code |
L01XX03 |
| PubChem |
CID: 2123 |
| IUPHAR/BPS |
7112 |
| DrugBank |
DB00488 Y |
| ChemSpider |
2038 Y |
| UNII |
Q8BIH59O7H Y |
| KEGG |
D02841 Y |
| ChEBI |
CHEBI:24564 Y |
| ChEMBL |
CHEMBL1455 Y |
| Chemical data |
| Formula |
C9H18N6 |
| Molecular mass |
210.28 g/mol |
SMILES
-
n1c(nc(nc1N(C)C)N(C)C)N(C)C
|
InChI
-
InChI=1S/C9H18N6/c1-13(2)7-10-8(14(3)4)12-9(11-7)15(5)6/h1-6H3 Y
-
Key:UUVWYPNAQBNQJQ-UHFFFAOYSA-N Y
|
| (verify) |
Altretamine (also hexalen) is an antineoplastic agent. It was approved by the FDA in 1990.
Contents
- 1 Uses
- 2 Mechanism
- 3 Side effects
- 4 Interactions
- 5 See also
- 6 References
Uses
It is used to treat refractory ovarian cancer.
It is not considered a first-line treatment,[1] but it can be useful as salvage therapy.[2] It also has the advantage of being less toxic than other drugs used for treating refractory ovarian cancer.[3]
Mechanism
The precise mechanism by which altretamine exerts its anti-cancer effect is unknown but it is classified by MeSH as an alkylating antineoplastic agent.[4] 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.[5]
Side effects
Side effects include nausea, vomiting, anemia and peripheral sensory neuropathy.[6]
Interactions
Combination with pyridoxine (vitamin B6) decreases neurotoxicity but has been found to reduce the effectiveness of an altretamine/cisplatin regime.[7] MAO inhibitor can cause severe orthostatic hypotension when combined with altretamine; and cimetidine can increase its elimination half-life and toxicity.[6]
See also
References
- ^ Keldsen N, Havsteen H, Vergote I, Bertelsen K, Jakobsen A (2003). "Altretamine (hexamethylmelamine) in the treatment of platinum-resistant ovarian cancer: a phase II study". Gynecol. Oncol. 88 (2): 118–22. doi:10.1016/S0090-8258(02)00103-8. PMID 12586589.
- ^ Chan JK, Loizzi V, Manetta A, Berman ML (2004). "Oral altretamine used as salvage therapy in recurrent ovarian cancer". Gynecol. Oncol. 92 (1): 368–71. doi:10.1016/j.ygyno.2003.09.017. PMID 14751188.
- ^ Malik IA (2001). "Altretamine is an effective palliative therapy of patients with recurrent epithelial ovarian cancer". Jpn. J. Clin. Oncol. 31 (2): 69–73. doi:10.1093/jjco/hye012. PMID 11302345.
- ^ Damia G, D'Incalci M (1995). "Clinical pharmacokinetics of altretamine". Clinical pharmacokinetics 28 (6): 439–48. doi:10.2165/00003088-199528060-00002. PMID 7656502.
- ^ "Foy`s principles of Medical chemistry", edited by Thomas L. Lemke, sixth edition, 2008, 1162 pages, ISBN 978-0-7817-6879-5.
- ^ a b Drugs.com: Altretamine Monograph
- ^ Wiernik, P. H.; Yeap, B.; Vogl, S. E.; Kaplan, B. H.; Comis, R. L.; Falkson, G.; Davis, T. E.; Fazzini, E.; Cheuvart, B.; Horton, J. (1992). "Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: A study of the Eastern Cooperative Oncology Group". Cancer investigation 10 (1): 1–9. doi:10.3109/07357909209032783. PMID 1735009.
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Pharmacokinetic study of solid-lipid-nanoparticles of altretamine complexed epichlorohydrin-β-cyclodextrin for enhanced solubility and oral bioavailability.
- Gidwani B1, Vyas A2.
- International journal of biological macromolecules.Int J Biol Macromol.2017 Aug;101:24-31. doi: 10.1016/j.ijbiomac.2017.03.047. Epub 2017 Mar 14.
- PMID 28315435
- Preparation, characterization, and optimization of altretamine-loaded solid lipid nanoparticles using Box-Behnken design and response surface methodology.
- Gidwani B1, Vyas A1.
- Artificial cells, nanomedicine, and biotechnology.Artif Cells Nanomed Biotechnol.2016;44(2):571-80. doi: 10.3109/21691401.2014.971462. Epub 2014 Nov 3.
- PMID 25363752
- Elucidating Compound Mechanism of Action by Network Perturbation Analysis.
- Woo JH1, Shimoni Y2, Yang WS3, Subramaniam P2, Iyer A2, Nicoletti P2, Rodríguez Martínez M2, López G2, Mattioli M4, Realubit R5, Karan C5, Stockwell BR6, Bansal M7, Califano A8.
- Cell.Cell.2015 Jul 16;162(2):441-451. doi: 10.1016/j.cell.2015.05.056.
- PMID 26186195
Japanese Journal
- Synthesis of Reactive s-Triazines Bearing a Cage System Derived from Adamantane as Precursors of Hexamethylmelamine Analogues
- In Vitro Cytotoxicity of Imidazolyl-1, 3, 5-triazine Derivatives
- In vivo Antitumor Activity of Hexamethylmelamine against Human Breast, Stomach and Colon Carcinoma Xenografts
- Japanese journal of cancer research : gann 86(8), 770-775, 1995-08-31
- NAID 10008069617
Related Links
- "Altretamine (hexamethylmelamine) in the treatment of platinum-resistant ovarian cancer: a phase II study". ... "Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: A ...
- Hexamethylmelamine. Generic name: Altretamine Trade names: Hexalen ® Other names: HMM. Chemocare.com uses generic names in all descriptions of drugs. Hexalen is the trade name for Altretamine. Hexamethylmelamine and HMM are ...
Related Pictures
★リンクテーブル★
[★]
隠れマルコフモデル
- 関
- hidden Markov model
- 関
- hexamethylmelamine
- 関
- See Heavy meromyosin
[★]
- 関
- hexamethylmelamine