AMINOPTERIN

US Previously Marketed

First approved in 1952

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H20N8O5
Molecular Weight	440.4127
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(N)=C2N=C(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=NC2=N1

InChI

InChIKey=TVZGACDUOSZQKY-LBPRGKRZSA-N

InChI=1S/C19H20N8O5/c20-15-14-16(27-19(21)26-15)23-8-11(24-14)7-22-10-3-1-9(2-4-10)17(30)25-12(18(31)32)5-6-13(28)29/h1-4,8,12,22H,5-7H2,(H,25,30)(H,28,29)(H,31,32)(H4,20,21,23,26,27)/t12-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C19H20N8O5
Molecular Weight	440.4127
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugbank.ca/drugs/DB08878
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00003305 | https://www.ncbi.nlm.nih.gov/pubmed/14206858 | https://clinicaltrials.gov/ct2/show/NCT01724931 |

Aminopterin is a synthetic derivative of pterins with antineoplastic and immunosuppressive properties. As a folate analog, aminopterin competes for the folate binding site of the enzyme dihydrofolate reductase, thereby blocking tetrahydrofolate synthesis, and resulting in depletion of nucleotide precursors and inhibition of DNA, RNA and protein synthesis. Aminopterin was marketed by Lederle Laboratories (Pearl River, New York) in the United States from 1953 to 1964 for the indication of pediatric leukemia. The closely related antifolate methotrexate was simultaneously marketed by the company during the same period. Aminopterin was discontinued by Lederle Laboratories in favor of methotrexate due to manufacturing difficulties of the former. During the period Aminopterin was marketed, the agent was used off-label to safely treat over 4,000 patients with psoriasis in the United States, producing dramatic clearing of lesions. The use of aminopterin in cancer treatment was supplanted in the 1950s by methotrexate due to the latter's better therapeutic index in a rodent tumor model. Now in a more pure preparation and supported by laboratory evidence of superior tumor cell uptake in vitro, aminopterin is being investigated in clinical trials in leukemia as a potentially superior antifolate to methotrexate.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydrofolate reductase 57 Target ID: CHEMBL202 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8035423	Inhibitor 8297		3.0 nM [IC50]
Folylpoly-gamma-glutamate synthetase 5 Target ID: CHEMBL3171 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12408727	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Pediatric leukemia 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18860765	Primary	Approved 8429	Unknown Approved Use Unknown
Acute lymphocytic leukemia 4 Sources: https://clinicaltrials.gov/ct2/show/NCT00176462	Primary	Phase II 1132	Unknown Approved Use Unknown
Rheumatoid arthritis 316 Sources: https://clinicaltrials.gov/ct2/show/record/NCT01724931	Primary	Phase II 1132	Unknown Approved Use Unknown
Endometrial cancer 43 Sources: https://clinicaltrials.gov/ct2/show/NCT00003821	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
0.166 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16299240	2 mg/m² 2 times / day multiple, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		AMINOPTERIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
0.51 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16299240	2 mg/m² 2 times / day multiple, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		AMINOPTERIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.2 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9552052	2 mg/m² 2 times / day multiple, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		AMINOPTERIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.64 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9552052	2 mg/m² 2 times / day multiple, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		AMINOPTERIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 mg 1 times / day multiple, oral Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6859892	unhealthy, adult n = 18 Health Status: unhealthy Condition: psoriasis \| indurative dermatoses Age Group: adult Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/6859892	Disc. AE: Buccal mucosa ulceration, Abdominal cramps... AEs leading to discontinuation/dose reduction: Buccal mucosa ulceration Abdominal cramps Sources: https://pubmed.ncbi.nlm.nih.gov/6859892
0.5 mg 1 times / day multiple, intramuscular Dose: 0.5 mg, 1 times / day Route: intramuscular Route: multiple Dose: 0.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18860765	unhealthy, child n = 1 Health Status: unhealthy Condition: acute leukemia Age Group: child Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18860765	Sources: https://pubmed.ncbi.nlm.nih.gov/18860765
1 mg 1 times / day multiple, intramuscular Dose: 1 mg, 1 times / day Route: intramuscular Route: multiple Dose: 1 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18860765	unhealthy, children n = 3 Health Status: unhealthy Condition: acute leukemia Age Group: children Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/18860765	Sources: https://pubmed.ncbi.nlm.nih.gov/18860765

AEs

AE	Significance	Dose	Population
Abdominal cramps	Disc. AE	2 mg 1 times / day multiple, oral Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6859892	unhealthy, adult n = 18 Health Status: unhealthy Condition: psoriasis \| indurative dermatoses Age Group: adult Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/6859892
Buccal mucosa ulceration	Disc. AE	2 mg 1 times / day multiple, oral Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6859892	unhealthy, adult n = 18 Health Status: unhealthy Condition: psoriasis \| indurative dermatoses Age Group: adult Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/6859892

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-071424	http://www.3bsc.com/index/pro_info.php?id=112498
AbMole Bioscience	M9787	http://www.abmole.com/products/aminopterin.html
Achemtek	0102-030658	http://www.achemtek.com/54-62-6
Adooq BioScience	A11787	https://www.adooq.com/aminopterin.html
Alfa Chemistry	AP54626	https://reagents.alfa-chemistry.com/product/aminopterin-cas-54-62-6-12907.html
Alfa Chemistry	AP54626-B	https://reagents.alfa-chemistry.com/product/aminopterin-ready-made-solution-cas-54-62-6-12909.html
Alfa Chemistry	AP54626-A	https://reagents.alfa-chemistry.com/product/methotrexate-related-compound-b-cas-54-62-6-12908.html
Aurora Fine Chemicals LLC	A17.875.835	http://online.aurorafinechemicals.com/info?ID=A17.875.835
Avantor Inc	TCA0410-100MG	https://us.vwr.com/store/product/16808786/aminopterin-hydrate-97-0-by-hplc-titration-analysis
Avantor Inc	TCA0410-25MG	https://us.vwr.com/store/product/16808786/aminopterin-hydrate-97-0-by-hplc-titration-analysis
BioSynth	A-7170	https://www.biosynth.com/en/products/life-science/culture-media-additives/products/A-7170.html
Chem Scene	CS-0003421	http://www.chemscene.com/54-62-6.html
ChemMol	99102373	http://www.chemmol.com/chemmol/99102373.html
Chemspace	CSSB00016999217	https://chem-space.com/CSSB00016999217
Glentham Life Sciences	GK2974	http://www.glentham.com/products/product/GK2974/
LGC Standards	MM0040.05	https://www.lgcstandards.com/US/en/p/MM0040.05
Lab Network	LN00193540	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00193540
MedChem Express	HY-14518	https://www.medchemexpress.com/aminopterin.html
Sigma-Aldrich	A1784_SIGMA	http://www.sigmaaldrich.com/catalog/product/SIGMA/A1784?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	A3411_SIGMA	http://www.sigmaaldrich.com/catalog/product/SIGMA/A3411?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	A5159_SIGMA	http://www.sigmaaldrich.com/catalog/product/SIGMA/A5159?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1414025_USP	http://www.sigmaaldrich.com/catalog/product/USP/1414025?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	SBR00016_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/sbr00016?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S518625	http://www.smolecule.com/products/s518625
Synblock Inc	SB17355	http://www.synblock.com/product/54-62-6.html
TCI (Tokyo Chemical Industry)	A0410	http://www.tcichemicals.com/eshop/en/us/commodity/A0410/index.html
THE BioTek	bt-259554	https://www.thebiotek.com/product/inhibitors/bt-259554
THE BioTek	bt-288622	https://www.thebiotek.com/product/others/bt-288622
abcr GmbH	AB473876	http://www.abcr.com/shop/en/AB473876
eNovation Chemicals	D404552	http://www.enovationchem.com/productDetails.asp?productID=D404552
iChemical	EBD24682	http://www.ichemical.com/chemicals/cas-54-62-6

PubMed

Title	Date	PubMed
On the mechanism of action of aminopterin.	1950 Jun	15440837
Activity of sulfa drugs and dihydrofolate reductase inhibitors against Candida albicans.	1982 Apr 15	7044814
Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.	1985 Sep-Oct	4029887
Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs.	1991 Jul	1929292
Inhibition of Pneumocystis dihydrofolate reductase by analogs of pyrimethamine, methotrexate and trimetrexate.	1991 Nov-Dec	1840146
Synthesis and biological activities of tricyclic conformationally restricted tetrahydropyrido annulated furo[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases.	1998 Apr 23	9554874
Developmental delay in fetal aminopterin/methotrexate syndrome.	1999 Jul	10413333
Fetal methotrexate and misoprostol exposure: the past revisited.	2002 Aug	12210010
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Phase II trial of oral aminopterin for adults and children with refractory acute leukemia.	2005 Nov 15	16299240
Fetal methotrexate/aminopterin syndrome in an adult: a likely case with ectodermal abnormalities.	2009 Jan	19011571
Pseudoaminopterin syndrome.	2012 Sep	22811276
Intestinal transport of aminopterin enantiomers in dogs and humans with psoriasis is stereoselective: evidence for a mechanism involving the proton-coupled folate transporter.	2012 Sep	22653877

Patents

Sample Use Guides

In Vivo Use Guide

1 or 3 mg aminopterin once weekly

Route of Administration: Oral

In Vitro Use Guide

CCRF-CEM human leukemic lymphoblasts were used for activity evaluation. In the growth inhibition assays, cells (5.5 × 104/mL) were incubated for 72 h in 24-well microtiter plates containing different concentrations of drugs (Aminopterin) (0.1-1000 nM in half-log increments) or in the absence of drug (negative controls). A 0.5-mL aliquot from each well was suspended in Isoton II (Fisher, Boston, MA) and cell numbers were determined with a hemocytometer after staining with trypan blue or eletronically with a Coulter model ZBI counter gated for a cell diameter of 10-30 µm

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:14:42 GMT 2023` Edited by `admin` on `Fri Dec 15 15:14:42 GMT 2023`
Record UNII	JYB41CTM2Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMINOPTERIN

Common Name

English

AMINOPTERIN [MI]

Common Name

English

METHOTREXATE IMPURITY B [EP IMPURITY]

Common Name

English

METHOTREXATE RELATED COMPOUND B

Common Name

English

Aminopterin [WHO-DD]

Common Name

English

4-AMINO-PGA

Common Name

English

AMINOTREXATE

Brand Name

English

N-(P-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)AMINO)BENZOYL)GLUTAMIC ACID

Common Name

English

N-(4-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)AMINO)BENZOYL)-L-GLUTAMIC ACID

Systematic Name

English

METHOTREXATE RELATED COMPOUND B [USP-RS]

Common Name

English

AMINOPTERIN [HSDB]

Common Name

English

NSC-739

Code

English

METHOTREXATE RELATED COMPOUND B [USP IMPURITY]

Common Name

English

4-AMINOFOLIC ACID

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2153