Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C9H18N6.ClH |
| Molecular Weight | 246.74 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CN(C)C1=NC(=NC(=N1)N(C)C)N(C)C
InChI
InChIKey=AKAQBNIEQUSIJL-UHFFFAOYSA-N
InChI=1S/C9H18N6.ClH/c1-13(2)7-10-8(14(3)4)12-9(11-7)15(5)6;/h1-6H3;1H
| Molecular Formula | C9H18N6 |
| Molecular Weight | 210.2794 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB00488Curator's Comment: Description was created based on several sources, including
http://www.rxlist.com/hexalen-drug/warnings-precautions.htm
http://www.survivorlibrary.com/library/anticancer-therapeutics.pdf#page=146
https://books.google.ru/books?hl=ru&lr=&id=VEibBwAAQBAJ&oi=fnd&pg=PP1&dq=Hexamethylmelamine+formaldehide&ots=-eXXGg_pDu&sig=H4nRJZrJvcJ4rK6AIQe68qCP_KI&redir_esc=y#v=onepage&q&f=false
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8456a8db-a7f6-4bc0-86be-e9c8c374140b
Sources: http://www.drugbank.ca/drugs/DB00488
Curator's Comment: Description was created based on several sources, including
http://www.rxlist.com/hexalen-drug/warnings-precautions.htm
http://www.survivorlibrary.com/library/anticancer-therapeutics.pdf#page=146
https://books.google.ru/books?hl=ru&lr=&id=VEibBwAAQBAJ&oi=fnd&pg=PP1&dq=Hexamethylmelamine+formaldehide&ots=-eXXGg_pDu&sig=H4nRJZrJvcJ4rK6AIQe68qCP_KI&redir_esc=y#v=onepage&q&f=false
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8456a8db-a7f6-4bc0-86be-e9c8c374140b
Altretamine is structurally similar to the alkylating agent triethylenemelamine (tretamine). Although Altretamine structurally resembles an alkylating agent, it has not been found to have alkylating activity in vitro. The precise mechanism of Altretamine cytotoxicity is unknown, although several proposals have been made. Altretamine requires N-demethylation in the liver to produce reactive intermediates (formaldehyde and/or iminium species) which covalently bind to DNA, resulting in DNA damage, or act as alkylating agents. Altretamine is used as a palliative treatment for persistent or recurrent ovarian cancer following treatment failure with a cisplatin- or alkylating agent-based combination. Side effects of Altretamine include nausea and vomiting, neurotoxicity (mood disorders, disorders of consciousness, ataxia, dizziness, vertigo), mild to moderate dose-related myelosuppression. Altretamine has been shown to be embryotoxic and teratogenic in rats and rabbits and may cause fetal damage when administered to a pregnant woman. Under the trade name Hexalen, Altretamine, is an antineoplastic agent. 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 a cisplatin and/or alkylating agent-based combination.
CNS Activity
Curator's Comment: Altretamine itself has poor CNS penetration. Its demethylated metabolites occur in high concentrations in cerebrospinal fluid and may be concentrated in the brain. Altretamine side effects include central neurotoxicity (rare) and peripheral neurotoxicity.
Additional resources:
https://books.google.ru/books?id=rRP-Wvc5uDgC&pg=PA89&lpg=PA89&dq=altretamine+blood+brain+barrier&source=bl&ots=V11TobJZil&sig=jAHs-S6mwG8qRRIHq1u185BIRuA&hl=ru&sa=X&sqi=2&ved=0ahUKEwiz1pfW5NbLAhUlAHMKHY-DDwgQ6AEITjAH#v=onepage&q=altretamine%20blood%20brain%20barrier&f=false
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Palliative | HEXALEN Approved UseINDICATIONS and USAGE HEXALEN® (altretamine) capsules 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 a cisplatin and/or alkylating agent-based combination. Launch Date1990 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
790 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2515524 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ALTRETAMINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1147 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2515524 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ALTRETAMINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2515524 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ALTRETAMINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
6% |
ALTRETAMINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
Other AEs: Granulocytopenia, Anxiety... Other AEs: Granulocytopenia (grade 4, 2 patients) Sources: Anxiety (grade 4, 1 patient) Depression (grade 4, 1 patient) Malaise (grade 3, 7%) Fatigue (grade 3, 7%) Lethargy (grade 3, 7%) Nausea (grade 3, 6%) Vomiting (grade 3, 3%) Paresthesia (grade 3, 1 patient) |
630 mg/m2 1 times / day multiple, parenteral MTD Dose: 630 mg/m2, 1 times / day Route: parenteral Route: multiple Dose: 630 mg/m2, 1 times / day Sources: |
unhealthy, adult |
|
850 mg/m2 single, parenteral MTD Dose: 850 mg/m2 Route: parenteral Route: single Dose: 850 mg/m2 Sources: |
unhealthy, adult |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Paresthesia | grade 3, 1 patient | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
| Vomiting | grade 3, 3% | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
| Nausea | grade 3, 6% | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
| Fatigue | grade 3, 7% | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
| Lethargy | grade 3, 7% | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
| Malaise | grade 3, 7% | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
| Anxiety | grade 4, 1 patient | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
| Depression | grade 4, 1 patient | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
| Granulocytopenia | grade 4, 2 patients | 260 mg/m2 1 times / day multiple, oral Recommended Dose: 260 mg/m2, 1 times / day Route: oral Route: multiple Dose: 260 mg/m2, 1 times / day Sources: |
unhealthy, 62.0 years (range: 33–81 years) n = 97 Health Status: unhealthy Condition: Epithelial Ovarian Cancer Age Group: 62.0 years (range: 33–81 years) Sex: F Population Size: 97 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Single-agent chemotherapy for recurrent carcinoma of the cervix. | 1980 |
|
| Hexamethylmelamine chemotherapy for disseminated endometrial cancer. | 1981 Sep |
|
| Orthostatic hypotension as a complication of hexamethylmelamine antidepressant interaction. | 1983 May |
|
| Incidence of neuropathy in 395 patients with ovarian cancer treated with or without cisplatin. | 1990 Oct 15 |
|
| The w/w+ SMART is a useful tool for the evaluation of pesticides. | 1994 Jul |
|
| Clinical pharmacokinetics of altretamine. | 1995 Jun |
|
| A rapid and systematic review of the clinical effectiveness and cost-effectiveness of topotecan for ovarian cancer. | 2001 |
|
| A phase I study of paclitaxel and altretamine as second-line therapy to cisplatin regimens for ovarian cancer. | 2001 Aug |
|
| Part II: chemotherapy for epithelial ovarian cancer-treatment of recurrent disease. | 2002 Sep |
|
| Altretamine (hexamethylmelamine) in the treatment of platinum-resistant ovarian cancer: a phase II study. | 2003 Feb |
|
| Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma. | 2003 Jul 3 |
|
| Lessons from a time capsule: evolution, not revolution, in therapy for advanced non-small-cell lung cancer. | 2008 Jul 1 |
|
| Relationship between frailty and cognitive decline in older Mexican Americans. | 2008 Oct |
|
| Liposomes incorporating sodium deoxycholate for hexamethylmelamine (HMM) oral delivery: development, characterization, and in vivo evaluation. | 2010 Apr |
Sample Use Guides
HEXALEN® (altretamine) capsules are administered orally. Doses are calculated on the basis of body surface area.
HEXALEN® (altretamine) capsules may be administered either for 14 or 21 consecutive days in a 28-day cycle at a dose of 260 mg/m²/day. The total daily dose should be given as 4 divided oral doses after meals and at bedtime.
Route of Administration:
Oral
In Vitro Use Guide
Curator's Comment: Hexamethylmelamine inhibited colony formation when incubated with A204 cells for 1 hour (short-term exposure) in the presence of the hepatic metabolizing system (S-9).
Long-term (10-day) exposure of Hexamethylmelamine (Altretamine) inhibited colony formation by human rhabdomyosarcoma cell line A204 by 70% at a concentration of 150 ug/ml.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 18:12:16 GMT 2023
by
admin
on
Fri Dec 15 18:12:16 GMT 2023
|
| Record UNII |
30FQ7QG6VM
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
2975-00-0
Created by
admin on Fri Dec 15 18:12:16 GMT 2023 , Edited by admin on Fri Dec 15 18:12:16 GMT 2023
|
PRIMARY | |||
|
30FQ7QG6VM
Created by
admin on Fri Dec 15 18:12:16 GMT 2023 , Edited by admin on Fri Dec 15 18:12:16 GMT 2023
|
PRIMARY | |||
|
DTXSID80183901
Created by
admin on Fri Dec 15 18:12:16 GMT 2023 , Edited by admin on Fri Dec 15 18:12:16 GMT 2023
|
PRIMARY | |||
|
27305
Created by
admin on Fri Dec 15 18:12:16 GMT 2023 , Edited by admin on Fri Dec 15 18:12:16 GMT 2023
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
PARENT -> SALT/SOLVATE |
