Altretamine
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MedKoo CAT#: 100040

CAS#: 645-05-6 (free base)

Description: Altretamine is a synthetic cytotoxic s-triazine derivative similar in structure to alkylating agent triethylenemelamin with antineoplastic activity. Although the precise mechanism by which altretamine exerts its cytotoxic effect is unknown, N-demethylation of altretamine may produce reactive intermediates which covalently bind to DNA, resulting in DNA damage. Check for active clinical trials or closed clinical trials using this agent.


Chemical Structure

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Altretamine
CAS# 645-05-6 (free base)

Theoretical Analysis

MedKoo Cat#: 100040
Name: Altretamine
CAS#: 645-05-6 (free base)
Chemical Formula: C9H18N6
Exact Mass: 210.15929
Molecular Weight: 210.28
Elemental Analysis: C, 51.41; H, 8.63; N, 39.97

Size Price Shipping out time Quantity
50mg USD 250 2 Weeks
100mg USD 450 2 Weeks
200mg USD 650 2 Weeks
500mg USD 1250 2 Weeks
1g USD 1850 2 Weeks
2g USD 2650 2 Weeks
5g USD 3650 2 Weeks
Inquire bulk and customized quantity

Pricing updated 2021-03-07. Prices are subject to change without notice.

Altretamine, purity > 98%, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Related CAS #: 2975-00-0 (HCl)   645-05-6 (free base)    

Synonym: Hemel; Hexaloids. US brand names: Hexalen; hexamethylmelamine. Foreign brand names: Hexastat; Hexinawas; Abbreviations: HMM; HXM. Code names: ENT50852; RB1515; WR95704.

IUPAC/Chemical Name: N2,N2,N4,N4,N6,N6-hexamethyl-1,3,5-triazine-2,4,6-triamine

InChi Key: UUVWYPNAQBNQJQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C9H18N6/c1-13(2)7-10-8(14(3)4)12-9(11-7)15(5)6/h1-6H3

SMILES Code: CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1

Appearance:
White to off-white solid powder.

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code:
2934.99.9001

Handling Instructions:

Preparing Stock Solutions

The following data is based on the product molecular weight 210.28 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Kelner MJ, McMorris TC, Rojas RJ, Estes LA, Suthipinijtham P. Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model. Cancer Chemother Pharmacol. 2008 Dec;63(1):19-26. doi: 10.1007/s00280-008-0703-0. Epub 2008 Feb 28. PubMed PMID: 18305940.

2: Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. PubMed PMID: 15086720.

3: 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 PMID: 14751188.

4: 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 PMID: 12586589.

5: Olver I, Davy M, Lüftner D, Park SH, Egorin M, Ellis A, Webster L. A phase I study of paclitaxel and altretamine as second-line therapy to cisplatin regimens for ovarian cancer. Cancer Chemother Pharmacol. 2001 Aug;48(2):109-14. PubMed PMID: 11561776.

6: Zon RT, McClean J, Helman D, Ansari R, Picus J, Sandler A, Williams SD, Loehrer PJ Sr. Altretamine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group trial. Invest New Drugs. 2001;19(3):229-31. PubMed PMID: 11561679.

7: Rothenberg ML, Liu PY, Wilczynski S, Hannigan EV, Weiner SA, Weiss GR, Hunter VJ, Chapman JA, Tiersten A, Kohler PC, Alberts DS. Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326). Gynecol Oncol. 2001 Aug;82(2):317-22. PubMed PMID: 11531286.

8: 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 PMID: 11302345.

9: Gershanovich ML, Livshits ME, Antipenkova VI. [Combination chemotherapy with hexamethylamine (Hexalen, Altretamine, Hexastat) and sarcolysine in advanced ovarian carcinoma]. Vopr Onkol. 2000;46(5):604-7. Russian. PubMed PMID: 11202196.

10: Markman M, Blessing JA, Moore D, Ball H, Lentz SS. Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 1998 Jun;69(3):226-9. PubMed PMID: 9648592.
   



Additional Information

Altretamine is a synthetic cytotoxic s-triazine derivative similar in structure to alkylating agent triethylenemelamin with antineoplastic activity. Although the precise mechanism by which altretamine exerts its cytotoxic effect is unknown, N-demethylation of altretamine may produce reactive intermediates which covalently bind to DNA, resulting in DNA damage. Altretamine  was approved by the FDA in 1990.
 
DRUG DESCRIPTION
HEXALEN® (altretamine) capsules, is a synthetic cytotoxic antineoplastic s-triazine derivative. HEXALEN® capsules contain 50 mg of altretamine for oral administration. Inert ingredients include lactose, anhydrous and calcium stearate. Altretamine, known chemically as N,N,N',N',N“,N”-hexamethyl-1,3,5-triazine-2,4,6-triamine. Its empirical formula is C9H18N6 with a molecular weight of 210.28. Altretamine is a white crystalline powder, melting at 172°± 1°C. Altretamine is practically insoluble in water but is increasingly soluble at pH 3 and below.
 
CLINICAL PHARMACOLOGY
The precise mechanism by which HEXALEN® capsules exerts its cytotoxic effect is unknown, although a number of theoretical possibilities have been studied. Structurally, HEXALEN® capsules resembles the alkylating agent triethylenemelamine, yet in vitro tests for alkylating activity of HEXALEN® capsules and its metabolites have been negative. HEXALEN® capsules has been demonstrated to be efficacious for certain ovarian tumors resistant to classical alkylating agents. Metabolism of altretamine is a requirement for 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. HEXALEN® capsules is well-absorbed following oral administration in humans, but undergoes rapid and extensive demethylation in the liver, producing variation in altretamine plasma levels. The principal metabolites are pentamethylmelamine and tetramethylmelamine. Pharmacokinetic studies were performed in a limited number of patients and should be considered preliminary. After oral administration of HEXALEN® capsules to 11 patients with advanced ovarian cancer in doses of 120-300 mg/m², peak plasma levels (as measured by gas-chromatographic assay) were reached between 0.5 and 3 hours, varying from 0.2 to 20.8 mg/l. Half-life of the β-phase of elimination ranged from 4.7 to 10.2 hours. Altretamine and metabolites show binding to plasma proteins. The free fractions of altretamine, pentamethylmelamine and tetramethylmelamine are 6%, 25% and 50%, respectively. Following oral administration of 14C-ring-labeled altretamine (4 mg/kg), urinary recovery of radioactivity was 61% at 24 hours and 90% at 72 hours. Human urinary metabolites were Ndemethylated homologues of altretamine with <1% unmetabolized altretamine excreted at 24 hours. After intraperitoneal administration of 14C-ring-labeled altretamine to mice, tissue distribution was rapid in all organs, reaching a maximum at 30 minutes. The excretory organs (liver and kidney) and the small intestine showed high concentrations of radioactivity, whereas relatively low concentrations were found in other organs, including the brain. There have been no formal pharmacokinetic studies in patients with compromised hepatic and/or renal function, though HEXALEN® capsules has been administered both concurrently and following nephrotoxic drugs such as cisplatin. HEXALEN® capsules has been administered in 4 divided doses, with meals and at bedtime, though there is no pharmacokinetic data on this schedule nor information from formal interaction studies about the effect of food on its bioavailability or pharmacokinetics. In two studies in patients with persistent or recurrent ovarian cancer following first-line treatment with cisplatin and/or alkylating agent-based combinations, HEXALEN® capsules was administered as a single agent for 14 or 21 days of a 28 day cycle. In the 51 patients with measurable or evaluable disease, there were 6 clinical complete responses, 1 pathologic complete response, and 2 partial responses for an overall response rate of 18%. The duration of these responses ranged from 2 months in a patient with a palpable pelvic mass to 36 months in a patient who achieved a pathologic complete response. In some patients, tumor regression was associated with improvement in symptoms and performance status.