Mycophenolic acid and its mechanism of action in cancer and psoriasis.
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.
D000818:Animals; D000877:Anthranilate Phosphoribosyltransferase / Q000378:metabolism; D001665:Binding Sites; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D005260:Female; D005965:Glucuronates / Q000096:biosynthesis; D005966:Glucuronidase / Q000378:metabolism; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D008658:Inactivation, Metabolic; D051379:Mice; D009173:Mycophenolic Acid / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology; D011565:Psoriasis / Q000188:drug therapy*; D051381:Rats
D005965:Glucuronates; D007168:IMP Dehydrogenase; D064429:Fatty Acid Synthases; D000877:Anthranilate Phosphoribosyltransferase; D005966:Glucuronidase; D009173:Mycophenolic Acid