Exploring the Diverse Uses of Aminopterin: From Leukemia Treatment to Cell Culture
Aminopterin,cas: 54-62-6 also
known as 4-aminopteroic acid, is a synthetic derivative of pterin and a 4-amino
derivative of folic acid. It is an antineoplastic drug with immunosuppressive
properties, often used in chemotherapy. Aminopterin functions as an enzyme
inhibitor by competing for the folate binding site of the enzyme dihydrofolate
reductase, effectively blocking tetrahydrofolate synthesis. This leads to the
depletion of nucleotide precursors and the inhibition of DNA, RNA, and protein
synthesis.Discovered by
Yellapragada Subbarow, Aminopterin was first used by Sidney Farber in 1947 to
induce remissions among children with leukemia. It was later marketed by
Lederle Laboratories in the United States from 1953 to 1964 for the treatment
of pediatric leukemia. During this time, it was also used off-label to treat
over 4,000 patients with psoriasis, producing dramatic clearing of lesions.
However,
Aminopterin's use in cancer treatment was supplanted by methotrexate in the
1950s due to the latter's better therapeutic index in a rodent tumor model.
Despite this, Aminopterin is now being investigated in clinical trials in
leukemia as a potentially superior antifolate to methotrexate, supported by
laboratory evidence of superior tumor cell uptake in vitro.
Aminopterin was
also explored as an abortifacient in the 1960s, but was associated with
congenital malformations. Similar congenital abnormalities have been documented
with methotrexate, and collectively their teratogenic effects have become known
as the fetal aminopterin syndrome. Aminopterin is widely used in selection
media, such as HAT medium, for cell culture, particularly in the development of
hybridomas, which secrete monoclonal antibodies.
In conclusion,
Aminopterin has played a significant role in the history of cancer treatment
and cell culture. Its impact on inducing remissions in children with leukemia
and its off-label use in treating psoriasis demonstrate its therapeutic
potential. Furthermore, ongoing research into its potential as a superior
antifolate to methotrexate in leukemia treatment highlights its enduring
relevance in the field of oncology.
Other information about Aminopterin:
(1)Aminopterin is a synthetic derivative of
pterin and a 4-amino derivative of folic acid. It functions as an enzyme
inhibitor by competing for the folate binding site of the enzyme dihydrofolate
reductase (DHFR), effectively blocking tetrahydrofolate synthesis. This leads
to the depletion of nucleotide precursors and the inhibition of DNA, RNA, and
protein synthesis.
(2)The uses of aminopterin include its
historical role in inducing remissions in children with leukemia, as well as
its off-label use in treating psoriasis. It is also being investigated in
clinical trials as a potentially superior antifolate to methotrexate in
leukemia treatment.
(3)Aminopterin syndrome refers to the
congenital malformations associated with the use of aminopterin and similar
antifolates. This includes teratogenic effects known as the fetal aminopterin
syndrome.
(4)Aminopterin in HAT
(hypoxanthine-aminopterin-thymidine) medium inhibits the growth of cells that
have not undergone somatic cell hybridization, making it useful in the
development of hybridomas for the production of monoclonal antibodies.