Peter,
There are, apparently, analogues of Camptothecin which offer a closer murine-human match, with regard to the time interval that the lactone ring remains closed. The following abstract is interesting (other relevant abstracts can be found through a CANCERLIT search for "camptothecin lactone.")
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Title
Alkyl esters of camptothecin and 9-nitrocamptothecin: synthesis, in vitro pharmacokinetics, toxicity, and antitumor activity.
Author
Cao Z; Harris N; Kozielski A; Vardeman D; Stehlin JS; Giovanella B
Address
Stehlin Foundation for Cancer Research, Houston, Texas 77003, USA.
Source
J Med Chem, 1998 Jan, 41:1, 31-7
Abstract
Eleven camptothecin esters, 6a-e and 7a-f, were prepared by straightforward acylation of camptothecins with the corresponding acylating reagents such as organic anhydrides and carboxylic acid chlorides. The in vitro pharmacokinetic determination of lactone levels of esters 6a and 7b showed that the biological life span of their lactone forms in human and mouse plasma significantly increased when compared with their mother compounds, camptothecin (3) and nitrocamptothecin (4). The differences of lactone levels between human plasma and mouse plasma for 6a and 7b were much smaller than what was observed for their mother compounds. The in vivo antitumor activity and toxicity studies demonstrated that some of these esters were very active against human tumor xenografts in nude mice and had an exceptional lack of toxicity in nude mice, even at enormous doses.
Language of Publication
English
Unique Identifier
98100831
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My question is, How to untangle the web of patents and licenses that surround these compounds? RFS 2000 certainly looks interesting (barring a total collapse in PIII, I have to believe that it should sail right through the FDA.) The next generation of Camptothecin analogues, however, appears to be even more promising, potentially. Only, who has the rights to these compounds? RTI? BMY? Stehlin? IDEC? SUPG?
Thanks,
RB |
