Aminopterin

Names

[ CAS No. ]:
54-62-6

[ Name ]:
Aminopterin

[Synonym ]:
4-Aminopteroyl-L-glutamic acid
L-Glutamic acid, N-(4-(((2,4-diamino-6-pteridinyl)methyl)amino)benzoyl)-
L-Glutamic acid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]amino]benzoyl]-
apga
4-AMINO-PGA
N-(4-{[(2,4-Diamino-6-pteridinyl)methyl]amino}benzoyl)-L-glutamic acid
4-Aminofolic acid
MFCD00036692
N-(4-{[(2,4-Diaminopteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acid
AGPA
EINECS 200-209-9
UNII-JYB41CTM2Q
Aminoperin
4-aminopteroylglutamic acid
aminopteridin
Aminopterin
L-N-[p-[[(2,4-diamino-6-pteridinyl)methyl]amino]benzoyl]-Glutamic acid
N-[4-[[(2,4-diamino-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid
Minopterin
pteramina

Biological Activity

[Description]:

Aminopterin (4-Aminofolic acid), the 4-amino derivative of folic acid, is a folic acid antagonist. Aminopterin catalyses the reduction of folic acid to tetrahydrofolic acid, and competitively inhibits dihydrofolate reductase (DHFR) with a Ki of 3.7 pM. Aminopterin has anticancer and immunosuppressive activity. Aminopterin is used in treatment of pediatric leukemia[1][2].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Antifolate

Research Areas >> Inflammation/Immunology

[In Vitro]

The IC50 value of Aminopterin (4-Aminofolic acid) against CCRF-CEM cells during 72 h of exposure is 4.4 nM[2]. Aminopterin (4-Aminofolic acid) produces a marked inhibition of mitosis in low concentrations in human leukemic leukocytes[4].

[References]

[1]. MEYER LM, et al. Aminopterin, a folic acid antagonist, in the treatment of leukemia. Am J Clin Pathol. 1949 Feb;19(2):119-26.

[2]. Rosowsky A, et al. Synthesis and in vitro antifolate activity of rotationally restricted aminopterin and methotrexate analogues. J Med Chem. 2004 Dec 30;47(27):6958-63.

[3]. Gebhardt DO, et al. The influence of aminopterin on limb regeneration in Ambystoma mexicanum. J Embryol Exp Morphol. 1966 Aug;16(1):143-58.

[4]. F. W Gtmrz, et al. THE EFFECT OF 4-AMINO-PTEROYLGLUTAMIC ACID (AMINOPTERIN) ON HUMAN LEUKEMIC LEUKOCYTES IN VITRO. Blood (1950) 5 (2): 161-166.

Chemical & Physical Properties

[ Density]:
1.6±0.1 g/cm3

[ Melting Point ]:
228-235 °C (dec.)

[ Molecular Formula ]:
C₁₉H₂₀N₈O₅

[ Molecular Weight ]:
440.413

[ Exact Mass ]:
440.155670

[ PSA ]:
219.33000

[ LogP ]:
-1.21

[ Index of Refraction ]:
1.762

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MA1050000

CHEMICAL NAME :: Glutamic acid, N-(p-(((2,4-diamino-6-pteridinyl)methyl)amino)benzoyl )-, L-

CAS REGISTRY NUMBER :: 54-62-6

BEILSTEIN REFERENCE NO. :: 0069045

LAST UPDATED :: 199701

DATA ITEMS CITED :: 56

MOLECULAR FORMULA :: C19-H20-N8-O5

MOLECULAR WEIGHT :: 440.47

WISWESSER LINE NOTATION :: T66 BN DN GN JNJ CZ EZ H1MR DVMYVQ2VQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 120 ug/kg

TOXIC EFFECTS :: Behavioral - anorexia (human) Gastrointestinal - other changes Skin and Appendages - hair

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2500 ug/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1900 ug/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 500 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1 mg/kg/10D-I

TOXIC EFFECTS :: Gastrointestinal - alteration in gastric secretion Gastrointestinal - hypermotility, diarrhea Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 246 ug/kg/5D-I

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Blood - changes in other cell count (unspecified) Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 24300 ug/kg/9D-I

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 22200 ug/kg/20D-I

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1200 ug/kg/17W-C

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Blood - leukemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 240 ug/kg

SEX/DURATION :: female 55-66 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 580 ug/kg

SEX/DURATION :: female 6-8 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2880 ug/kg

SEX/DURATION :: female 56-67 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - Apgar score (human only)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 165 ug/kg

SEX/DURATION :: female 40-44 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 188 ug/kg

SEX/DURATION :: female 54-55 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 151 ug/kg

SEX/DURATION :: female 35-36 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 240 ug/kg

SEX/DURATION :: female 1-30 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 240 ug/kg

SEX/DURATION :: female 53-55 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 15 ug/kg

SEX/DURATION :: female 1-3 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 150 ug/kg

SEX/DURATION :: female 9-11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 112 ug/kg

SEX/DURATION :: female 6 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 75 ug/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 200 ug/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 150 ug/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - homeostasis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 150 ug/kg

SEX/DURATION :: female 6 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 280 ug/kg

SEX/DURATION :: male 28 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 75 ug/kg

SEX/DURATION :: female 6 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 75 ug/kg

SEX/DURATION :: female 6 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 50 ug/kg

SEX/DURATION :: female 6 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 200 ug/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 3 mg/kg

SEX/DURATION :: female 1 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 2 mg/kg

SEX/DURATION :: female 14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 20 mg/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 20 mg/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - physical

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2500 ug/kg

SEX/DURATION :: female 18-27 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 500 ug/kg

SEX/DURATION :: female 18-27 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 500 ug/kg

SEX/DURATION :: female 16-25 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 300 ug/kg

SEX/DURATION :: female 20-22 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 15 mg/kg

SEX/DURATION :: female 15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1100 ug/kg

SEX/DURATION :: female 12-33 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: Micronucleus test

MUTATION DATA

TEST SYSTEM :: Rodent - mouse

DOSE/DURATION :: 2 mg/kg/5D

REFERENCE :: PNASA6 Proceedings of the National Academy of Sciences of the United States of America. (National Academy of Sciences, Printing & Pub. Office, 2101 Constitution Ave., Washington, DC 20418) V.1- 1915- Volume(issue)/page/year: 72,4425,1975 *** REVIEWS *** TOXICOLOGY REVIEW BCSTB5 Biochemical Society Transactions. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1973- Volume(issue)/page/year: 2,695,1974 TOXICOLOGY REVIEW PLMJAP Pahlavi Medical Journal. (Shiraz, Iran) V.1-9, 1970-78. Volume(issue)/page/year: 6,160,1975 TOXICOLOGY REVIEW JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 172,1765,1960 TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 TOXICOLOGY REVIEW JOGBAS Journal of Obstetrics and Gynaecology of the British Commonwealth. (London, UK) V.68-81, 1961-74. For publisher information, see BJOGAS. Volume(issue)/page/year: 75,307,1968 TOXICOLOGY REVIEW ARVPAX Annual Review of Pharmacology. (Palo Alto, CA) V.1-15, 1961-75. For publisher information, see ARPTDI. Volume(issue)/page/year: 5,447,1965 TOXICOLOGY REVIEW ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ. Volume(issue)/page/year: 4,263,1966 TOXICOLOGY REVIEW ATXKA8 Archiv fuer Toxikologie. (Berlin, Fed. Rep. Ger.) V.15-31, 1954-74. For publisher information, see ARTODN. Volume(issue)/page/year: 28,135,1971

Safety Information

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H300-H360

[ Precautionary Statements ]:
P201-P264-P301 + P310-P308 + P313

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
T+:Verytoxic;

[ Risk Phrases ]:
R61;R28

[ Safety Phrases ]:
S53-S28-S36/37-S45

[ RIDADR ]:
UN 2811 6.1/PG 1

[ WGK Germany ]:
3

[ RTECS ]:
MA1050000

[ Packaging Group ]:
I

[ Hazard Class ]:
6.1(a)

[ HS Code ]:
3822009000

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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Related Compounds

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