Back to the Top
Dear all,
we would like to assess the antitumoral effects of a pro-drug which
unfortunately is immediately activated by erythrocytic purine phosphorylase
(PNP), and therefore has little but no chance to reach the tumor to be
properly activated.
We are looking for erythrocyte-specific inhibitor of PNP that could spare
the prodrug and allow it to be fully distributed for eventually reaching
the tumor.
Has anybody heard about such drugs? Data from the literature suggest
several molecules (some of them being associated with anti HIV drug DDI,
which encounts similar problems of erythrocitic metabolism), but what we
need is a specific inhibitor which will act on erythrocitic but not tumoral
PNP activities.
If anyone has a clue, please let me know!
Thanks,
Pr. Jacques Catalin, Ph.D.
Laboratoire de Toxicocinetique et Pharmacocinetique
Faculte de Pharmacie
27, Bd Jean Moulin
13385 Marseille cedex 05
France
Phone: (33) (0)4 91 83 55 09
Fax: (33) (0)4 91 83 56 67
Back to the Top
Dear Dr. Catalin
I am not familiar with any inhibitor that would specifically inhibit
erythrocyte PNP, but I received this note from Dr. Varsha Gandhi at MD
Anderson Cancer Center in Houston, TX, USA.
At the AACR meeting (1999) there was one platform presentation that talked
about compounds called immucilin-H. These are actually purine analogs.
The sugar is modified with an NH group instead of O (oxygen). They have
two different immucilins; one with guanine base and other with adenine
base. Both these agents inhibit PNP with a Ki of 20 to 30 pM. I was not
completely convinced with the data to show PNP inhibition in whole cells
but nonetheless it was only a 10 min. talk. Hence my exposure to these
analogs is limited. The authors were showing that simultaneous incubation
with this agent and dGuo resulted in cytotoxicity which was mediated
through accumulation of high concentration of dGTP. The abstract citation
is Amer Assoc Cancer Res 40:622, 1999.
Good Luck!
David F. Kisor
Ohio Northern University
Back to the Top
can the prodrug be further protected to reduce/eliminate the possibility of non
target metabolism? By coupling it with tumor specific antibodies/ferrous
compounds?
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)