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Details

Stereochemistry ACHIRAL
Molecular Formula C9H18N6
Molecular Weight 210.2798
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALTRETAMINE

SMILES

CN(C)c1nc(nc(n1)N(C)C)N(C)C

InChI

InChIKey=UUVWYPNAQBNQJQ-UHFFFAOYSA-N
InChI=1S/C9H18N6/c1-13(2)7-10-8(14(3)4)12-9(11-7)15(5)6/h1-6H3

HIDE SMILES / InChI

Molecular Formula C9H18N6
Molecular Weight 210.2798
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Originator

Curator's Comment:: The synthesis of hexamethylmelamine (Altretamine) was first reported in 1951 (Kaiser et al., 1951).

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
HEXALEN

Approved Use

INDICATIONS 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 Date

6.6216958E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
790 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
1147 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
2.2 h
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

Funbound

ValueDoseCo-administeredAnalytePopulation
6%
ALTRETAMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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)
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)
Sources:
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
Health Status: unhealthy
Age Group: adult
Sources:
850 mg/m2 single, parenteral
MTD
Dose: 850 mg/m2
Route: parenteral
Route: single
Dose: 850 mg/m2
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Single-agent chemotherapy for recurrent carcinoma of the cervix.
1980
Hexamethylmelamine chemotherapy for disseminated endometrial cancer.
1981 Sep
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
Altretamine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group trial.
2001
A phase I study of paclitaxel and altretamine as second-line therapy to cisplatin regimens for ovarian cancer.
2001 Aug
Altretamine (hexamethylmelamine) in the treatment of platinum-resistant ovarian cancer: a phase II study.
2003 Feb
Oral melphalan as a treatment for platinum-resistant ovarian cancer.
2003 Jun 16
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.
2004 Mar-Apr
Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site.
2004 May 17
Recurrent ovarian cancer: how important is it to treat to disease progression?
2004 Nov 15
Emerging drugs for ovarian cancer.
2005 May
Topotecan: weighing in when there are many options.
2005 Oct
Better treatments improve survival of CHD patients.
2005 Sep
Pretreatment CA-125 and risk of relapse in advanced ovarian cancer.
2006 Mar 20
Atom efficient cyclotrimerization of dimethylcyanamide catalyzed by aluminium amide: a combined experimental and theoretical investigation.
2008 Aug 21
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.
2008 Dec
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
Clinical trials and progress with paclitaxel in ovarian cancer.
2010 Nov 19
Patents

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 Fri Jun 25 20:58:32 UTC 2021
Edited
by admin
on Fri Jun 25 20:58:32 UTC 2021
Record UNII
Q8BIH59O7H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALTRETAMINE
HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
ALTRETAMINE [HSDB]
Common Name English
1,3,5-TRIAZINE-2,4,6-TRIAMINE, N,N,N',N',N'',N''-HEXAMETHYL-
Systematic Name English
HEXAMETHYLMELAMINE
Common Name English
ALTRETAMINE [MI]
Common Name English
ALTRETAMINE [USP-RS]
Common Name English
ALTRETAMINE [MART.]
Common Name English
ALTRETAMINE [ORANGE BOOK]
Common Name English
NSC-13875
Code English
ALTRETAMINE [WHO-DD]
Common Name English
ALTRETAMINE [USAN]
Common Name English
HEXALEN
Systematic Name English
ALTRETAMINE [INN]
Common Name English
ALTRETAMINE [VANDF]
Common Name English
ALTRETAMINE [USP MONOGRAPH]
Common Name English
Classification Tree Code System Code
LIVERTOX 32
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
NCI_THESAURUS C292
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
FDA ORPHAN DRUG 983
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
NDF-RT N0000175558
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
WHO-VATC QL01XX03
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
WHO-ATC L01XX03
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
NDF-RT N0000000236
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
Code System Code Type Description
RXCUI
5296
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY RxNorm
HSDB
7559
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
ECHA (EC/EINECS)
211-428-4
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
CAS
645-05-6
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
MESH
D006585
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
DRUG BANK
DB00488
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
WIKIPEDIA
ALTRETAMINE
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
ChEMBL
CHEMBL1455
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
IUPHAR
7112
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
INN
4825
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
EVMPD
SUB05382MIG
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
EPA CompTox
645-05-6
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
FDA UNII
Q8BIH59O7H
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
MERCK INDEX
M1586
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
141
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
PUBCHEM
2123
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
NCI_THESAURUS
C544
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY
USP_CATALOG
1017105
Created by admin on Fri Jun 25 20:58:32 UTC 2021 , Edited by admin on Fri Jun 25 20:58:32 UTC 2021
PRIMARY USP-RS
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC