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Aminopterin was the first drug to send childhood leukaemia into remission. In 1948 Sidney Farber reported temporary remissions in children with acute leukaemia, the birth of cancer chemotherapy; its safer cousin methotrexate replaced it within a decade.
Aminopterin was synthesised at Lederle Laboratories after Sidney Farber observed that folic acid seemed to accelerate leukaemia in children and reasoned that a folate antagonist might do the opposite. In June 1948 Farber and colleagues reported in the New England Journal of Medicine that 10 of 16 children with acute leukaemia had temporary remissions on aminopterin, the first demonstration that a drug could reverse a cancer.
Its narrow margin between benefit and toxicity led to its replacement by methotrexate (amethopterin) in the 1950s, and it is no longer marketed. It is named on the acute lymphoblastic leukaemia pages as the founding drug of chemotherapy.
A folic acid analogue that blocks dihydrofolate reductase, starving dividing leukaemia cells of the reduced folate they need to make DNA; methotrexate, a methylated derivative, replaced it. Connects to Dihydrofolate reductase (DHFR).
1.Aminopterin slips into a pocket on Dihydrofolate reductase (DHFR).
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Query for this drug: (TITLE:"Aminopterin" OR ABSTRACT:"Aminopterin" OR TITLE:"4-aminopteroylglutamic acid" OR ABSTRACT:"4-aminopteroylglutamic acid") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Aminopterin, not a curated reading list.
Shares Methotrexate and the tag subtype-drugs-wave.
Shares Methotrexate, Acute lymphoblastic leukaemia, Cytotoxic chemotherapy.
Shares Methotrexate, Acute lymphoblastic leukaemia, Acute myeloid leukaemia, Cytotoxic chemotherapy.
Shares Standard-risk B-cell acute lymphoblastic leukaemia in children, Acute lymphoblastic leukaemia.
Shares Methotrexate, Acute lymphoblastic leukaemia, Cytotoxic chemotherapy.
Shares Methotrexate, Acute lymphoblastic leukaemia, Cytotoxic chemotherapy.
Shares Methotrexate, Acute lymphoblastic leukaemia, Cytotoxic chemotherapy.