Mycophenolic acid is active against fungi, bacteria, and viruses in vitro and is active against some viruses and
tumors in experimental animals.
Mycophenolic acid is not effective in the treatment of
cancer in man, but it is effective in treating
psoriasis. In all of the various diseases MA presumably inhibits the synthesis of GMP resulting in decreased synthesis of
RNA and
DNA. The direct inhibition of GMP synthesis is the result of MA activity against the IMPDHase and
GMP synthetase as determined in experimental
tumors. The inhibition of GMP synthesis can be circumvented by the
guanine salvage pathway which is controlled by PRTase activity. PRTase may be the sole factor in preventing the inhibition caused by MA in the biosynthesis of GMP (Fig. 3). However, before MA can stop GMP synthesis, MA must enter the cell. The current data show that MA is almost completely detoxified in man and circulates in the plasma as the
glucuronide, MAG,
Glucuronides are normally inactive forms of active drugs. Due to their bivalent and non-lipophilic nature,
glucuronides do not normally cross the cell membranes. Therefore, MAG is extracellular and beta-
Gase intracellular, and this prevents hydrolysis of MAG to the active MA in
cancer patients.