The role of folylpolyglutamates in biosynthetic processes has
gained increasing importance with the recognition that these com
pounds are not only the forms of folate co-factors that accumulate
within cells, but, in addition, are the preferred substrates for
folate dependent reactions in eukaryotic cells. More recently
attention has turned to the potential importance of the
polyglutamyl derivatives of methotrexate that have been detected in
normal and malignant cells both in vitro and in vivo. The
biochemical trans formation of this important chemotherapeutic
agent is of particular significance since polyglutamyl derivatives
of methotrexate are not only potent inhibitors of the target
enzyme, but have quite different cellular pharmacokinetics than the
parent monoglutamate. Hence, nearly three and a half decades after
4-aminoantifolates were first applied clinically in the treatment
of human neoplasms, we have begun to appreciate a new dimension in
antifolate pharmaco logy which may have profound implications for
our understanding of the mechanism of the cytotoxicity and
selectivity of this class of agents. With the development of highly
sensitive methodology for the rapid detection of folyl and
antifolyl polyglutamates, it is now possible to define in depth the
intracellular transformation of these agents and their role in
determining antifolate action against normal and malignant cells.
This information will very likely influence how regimens with
methotrexate and related antifolates will be further developed and
employed clinically."
General
| Imprint: |
Springer-Verlag New York
|
| Country of origin: |
United States |
| Series: |
Advances in Experimental Medicine and Biology, 163 |
| Release date: |
May 2013 |
| First published: |
1983 |
| Editors: |
I. David Goldman
|
| Dimensions: |
254 x 178 x 23mm (L x W x T) |
| Format: |
Paperback
|
| Pages: |
425 |
| Edition: |
Softcover reprint of the original 1st ed. 1983 |
| ISBN-13: |
978-1-4757-5243-4 |
| Categories: |
Books >
Medicine >
Other branches of medicine >
Pharmacology >
General
|
| LSN: |
1-4757-5243-1 |
| Barcode: |
9781475752434 |
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