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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H20N8O5
Molecular Weight 440.4134
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMINOPTERIN

SMILES

c1cc(ccc1C(=O)N[C@@]([H])(CCC(=O)O)C(=O)O)NCc2cnc3c(c(N)[nH]c(=N)n3)n2

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 440.4134
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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

Sources: Byulleten Eksperimental'noi Biologii i Meditsiny (1947), 23, 239-47.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.166 μM
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

AUC

ValueDoseCo-administeredAnalytePopulation
0.51 μM × h
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.64 h
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

Doses

DosePopulationAdverse 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:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: psoriasis | indurative dermatoses
Age Group: adult
Population Size: 18
Sources:
Disc. AE: Buccal mucosa ulceration, Abdominal cramps...
AEs leading to
discontinuation/dose reduction:
Buccal mucosa ulceration
Abdominal cramps
Sources:
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:
unhealthy, child
n = 1
Health Status: unhealthy
Condition: acute leukemia
Age Group: child
Sex: M
Population Size: 1
Sources:
1 mg 1 times / day multiple, intramuscular
Dose: 1 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 1 mg, 1 times / day
Sources:
unhealthy, children
n = 3
Health Status: unhealthy
Condition: acute leukemia
Age Group: children
Sex: M+F
Population Size: 3
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: psoriasis | indurative dermatoses
Age Group: adult
Population Size: 18
Sources:
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:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: psoriasis | indurative dermatoses
Age Group: adult
Population Size: 18
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
On the mechanism of action of aminopterin.
1950 Jun
Activity of sulfa drugs and dihydrofolate reductase inhibitors against Candida albicans.
1982 Apr 15
Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.
1985 Sep-Oct
Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs.
1991 Jul
Inhibition of Pneumocystis dihydrofolate reductase by analogs of pyrimethamine, methotrexate and trimetrexate.
1991 Nov-Dec
Synthesis and biological activities of tricyclic conformationally restricted tetrahydropyrido annulated furo[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases.
1998 Apr 23
Fetal methotrexate and misoprostol exposure: the past revisited.
2002 Aug
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Phase II trial of oral aminopterin for adults and children with refractory acute leukemia.
2005 Nov 15
Fetal methotrexate/aminopterin syndrome in an adult: a likely case with ectodermal abnormalities.
2009 Jan
Pseudoaminopterin syndrome.
2012 Sep
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
Patents

Patents

Sample Use Guides

1 or 3 mg aminopterin once weekly
Route of Administration: Oral
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 Sat Jun 26 02:49:15 UTC 2021
Edited
by admin
on Sat Jun 26 02:49:15 UTC 2021
Record UNII
JYB41CTM2Q
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMINOPTERIN
HSDB   MI   WHO-DD  
Common Name English
AMINOPTERIN [MI]
Common Name English
METHOTREXATE RELATED COMPOUND B
USP   USP-RS  
Common Name English
4-AMINO-PGA
Common Name English
AMINOTREXATE
Brand Name English
AMINOPTERIN [WHO-DD]
Common Name English
N-(P-(((2,4-DIAMINO-6-PTERIDINYL)METHYL)AMINO)BENZOYL)GLUTAMIC ACID
Common Name English
METHOTREXATE SPECIFIED IMPURITY B [EP]
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
4-AMINOFOLIC ACID
Common Name English
METHOTREXATE RELATED COMPOUND B [USP]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2153
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
NCI_THESAURUS C511
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C235
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-209-9
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
USP_CATALOG
1414025
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY USP-RS
DRUG CENTRAL
21
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
MERCK INDEX
M1738
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
AMINOPTERIN
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
RXCUI
1440264
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY RxNorm
FDA UNII
JYB41CTM2Q
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
CAS
54-62-6
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
EPA CompTox
54-62-6
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
HSDB
6374
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
DRUG BANK
DB08878
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
PUBCHEM
169371
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
MESH
D000630
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
EVMPD
SUB00464MIG
Created by admin on Sat Jun 26 02:49:16 UTC 2021 , Edited by admin on Sat Jun 26 02:49:16 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY