RS-61443: successful rescue therapy in refractory renal rejection.
RS-61443, the morpholinoethyl ester of mycophenolic acid (mPA), is a potent, noncompetitive, reversible inhibitor of eucaryotic inosine monophosphate (IMP) dehydrogenases. Because of the importance of the guanosine and deoxyguanosine nucleotides in activating phosphoribosyl pyrophosphate (PRPP) synthesis and ribonucleotide reductase, respectively, it was postulated that depletion of GMP (and consequently GTP and GDP) would have antiproliferative effects on lymphocytes. Furthermore, since lymphocytes rely on de novo pruine synthesis whereas other cell types do not, antiproliferative effects produced in this way are more selective for lymphocytes than other cell types.
Sollinger
H W
HW
Department of Surgery, University of Wisconsin, Madison, Wisconsin, USA.
Deierhoi
M H
MH
Kauffman
R S
RS
Diethelm
A G
AG
Belzer
F O
FO
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002102:Cadaver; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D016853:Muromonab-CD3 / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014019:Tissue Donors
D000305:Adrenal Cortex Hormones; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid