ALTRETAMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H18N6
Molecular Weight	210.2794
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)C1=NC(=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

Description
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: http://www.drugbank.ca/drugs/DB00488 \| https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8456a8db-a7f6-4bc0-86be-e9c8c374140b&type=display	Interacts 323

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ovarian cancer, persistent or recurrent 2 Sources: http://www.rxlist.com/hexalen-drug/indications-dosage.htm	Palliative		Approved 8429	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 1990

C_max

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

T_1/2

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

F_unbound

Value	Dose	Co-administered	Analyte	Population
6% OTHER GOV https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8456a8db-a7f6-4bc0-86be-e9c8c374140b			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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/2104537	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://pubmed.ncbi.nlm.nih.gov/2104537	Sources: https://pubmed.ncbi.nlm.nih.gov/2104537
850 mg/m2 single, parenteral MTD Dose: 850 mg/m2 Route: parenteral Route: single Dose: 850 mg/m2 Sources: https://pubmed.ncbi.nlm.nih.gov/2104537	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://pubmed.ncbi.nlm.nih.gov/2104537	Sources: https://pubmed.ncbi.nlm.nih.gov/2104537

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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286
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: https://pubmed.ncbi.nlm.nih.gov/11531286	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: https://pubmed.ncbi.nlm.nih.gov/11531286

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY565266	https://www.001chemical.com/chem/645-05-6
3B Scientific (Wuhan) Corp	3B2-0964	http://www.3bsc.com/index/pro_info.php?id=41869
AA Blocks	AA0034DG	https://www.aablocks.com/goods/Goods/detail?id=AA0034DG
AHH Chemical co.,ltd	MT-46992	http://www.ahhchemical.com/product/MT-46992.html
AK Scientific, Inc. (AKSCI)	65631	http://www.aksci.com/item_detail.php?cat=65631
Aaron Chemicals	AR003558	http://www.aaronchem.com/645-05-6
AbMole Bioscience	M2242	http://www.abmole.com/products/altretamine.html
Achemtek	0104-006567	http://www.achemtek.com/645-05-6
Active Biopharma	ABP000596	http://www.activebiopharma.com/645-05-6
Adooq BioScience	A10059	https://www.adooq.com/altretamine.html
Alfa Chemistry	AP645056	https://reagents.alfa-chemistry.com/product/altretamine-cas-645-05-6-14551.html
Ambeed	A112657	https://www.ambeed.com/products/645-05-6.html
Ambinter	Amb1007035	http://www.ambinter.com/reference/1007035
Angel Pharmatech	AG252110	http://www.angelpharmatech.com/645-05-6.html
Ark Pharm	AK431828	http://www.arkpharminc.com/products/645-05-6.html
Aurora Fine Chemicals LLC	A13.142.921	http://online.aurorafinechemicals.com/info?ID=A13.142.921
Aurora Fine Chemicals LLC	K01.093.554	http://online.aurorafinechemicals.com/info?ID=K01.093.554
Aurum Pharmatech LLC	M-2093	http://www.Aurumpharmatech.com/Product/ProductDetails/M_2093
BLD Pharm	BD66388	http://www.bldpharm.com/products/645-05-6.html
BioChemPartner	BCP27675	http://www.biochempartner.com/645-05-6-BCP27675
BioCrick	BCC1216	http://www.biocrick.com/Altretamine-BCC1216.html
BioSynth	J-523408	https://www.biosynth.com/en/products/all-products/products/J-523408.html
Boerchem	BC203873	http://www.boerchem.com/?product_34242.html
CSNpharm	CSN18706	https://www.csnpharm.com/products/altretamine.html
Chem Scene	CS-2061	http://www.chemscene.com/645-05-6.html
ChemBridge	5148727	http://www.hit2lead.com/search.asp?db=SC&ids=5148727
ChemMol	30101821	http://www.chemmol.com/chemmol/30101821.html
ChemMol	44001616	http://www.chemmol.com/chemmol/44001616.html
ChemMol	49428477	http://www.chemmol.com/chemmol/49428477.html
Chemenu	CM110241	http://www.chemenu.com/products/CM110241
Chemspace	CSSB00000016056	https://chem-space.com/CSSB00000016056
DC Chemicals	DCAPI1290	http://www.dcchemicals.com//product_show-Altretamine_Hexalen_.html
Debye Scientific	DB-054676	http://www.debyesci.com/cas_645-05-6.html
Enamine	Z57931197	https://www.enaminestore.com/catalog/Z57931197
Finetech	FT-0651499	http://www.finetechnology-ind.com/prod/detail/pub/645-05-6.html
Glentham Life Sciences	GP0509	http://www.glentham.com/products/product/GP0509/
Hairui	HR126599	http://www.hairuichem.com/en/product/645-05-6.html
Lab Network	LN00195151	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00195151
MedChem Express	HY-B0181	https://www.medchemexpress.com/Altretamine.html
Molcore	MC565266	https://www.molcore.com/product/645-05-6
OChem	249	http://www.ocheminc.com/index.php?act=psearch&pid=645A056
Oakwood	358119	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=197309&ExtHyperLink=1
Parchem	28163	http://www.parchem.com/chemical-supplier-distributor/Altretamine-018163.aspx
Renno Tech	RP18094	http://www.rennotech.com/product_show.asp?id=23962
Selleck Chemicals	S1278	http://www.selleckchem.com/products/Altretamine.html
Sigma-Aldrich	549835_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/549835?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	A8723_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/a8723?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1017105_USP	https://www.sigmaaldrich.com/catalog/product/usp/1017105?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S518191	http://www.smolecule.com/products/s518191
THE BioTek	bt-258581	https://www.thebiotek.com/product/inhibitors/bt-258581
THE BioTek	bt-318379	https://www.thebiotek.com/product/others/bt-318379
Vesino Industrial Co Ltd	VA10242	http://www.vsnchem.com/goto/product/23743/
Yuhao Chemical	JZ4099	http://www.chemyuhao.com/645-05-6.html
abcr GmbH	AB509262	http://www.abcr.com/shop/en/AB509262
eNovation Chemicals	D672618	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672618
eNovation Chemicals	D766181	https://www.enovationchem.com/ProductDetails.asp?ProductID=D766181
iChemical	EBD29031	http://www.ichemical.com/chemicals/cas-645-05-6
mcule	MCULE-1605383293	https://mcule.com/MCULE-1605383293/

PubMed

Title	Date	PubMed
Orthostatic hypotension as a complication of hexamethylmelamine antidepressant interaction.	1983 May	6406063
The w/w+ SMART is a useful tool for the evaluation of pesticides.	1994 Jul	7968576
Clinical pharmacokinetics of altretamine.	1995 Jun	7656502
Altretamine for the treatment of metastatic renal cell carcinoma. A Hoosier Oncology Group trial.	2001	11561679
Altretamine is an effective palliative therapy of patients with recurrent epithelial ovarian cancer.	2001 Feb	11302345
Part II: chemotherapy for epithelial ovarian cancer-treatment of recurrent disease.	2002 Sep	12217791
Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma.	2003 Jul 3	12841853
Oral melphalan as a treatment for platinum-resistant ovarian cancer.	2003 Jun 16	12799622
A phase II study of sequential carboplatin, paclitaxel and topotecan in patients with previously untreated advanced ovarian cancer.	2004 Feb 23	14970858
Topotecan: weighing in when there are many options.	2005 Oct	16249349
Pretreatment CA-125 and risk of relapse in advanced ovarian cancer.	2006 Mar 20	16549840
Atom efficient cyclotrimerization of dimethylcyanamide catalyzed by aluminium amide: a combined experimental and theoretical investigation.	2008 Aug 21	18665286
Lessons from a time capsule: evolution, not revolution, in therapy for advanced non-small-cell lung cancer.	2008 Jul 1	18591551
Relationship between frailty and cognitive decline in older Mexican Americans.	2008 Oct	18811611

Patents

Sample Use Guides

In Vivo Use Guide

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

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.

Name

Type

Language

ALTRETAMINE

Official Name

English

ALTRETAMINE [HSDB]

Common Name

English

Altretamine [WHO-DD]

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 [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

NBK548524