mycophenolate

Mycophenolate mofetil is a prodrug that is hydrolyzed to its active form, mycophenolic acid (MPA). MPA reversibly inhibits inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo purine synthesis pathway required for guanosine nucleotide production. Because T and B lymphocytes rely heavily on de novo purine synthesis (unlike other cell types that can use salvage pathways), mycophenolate selectively suppresses lymphocyte proliferation, reducing both cell-mediated and antibody-mediated immune responses.

Clinical uses: (1) Prevention of acute rejection in kidney, heart, and liver transplants, typically combined with a calcineurin inhibitor (tacrolimus/cyclosporine) and corticosteroids. (2) Treatment of autoimmune diseases such as lupus nephritis, and as a steroid-sparing agent in various autoimmune/inflammatory conditions (e.g., pemphigus, vasculitis).

Adverse effects: GI toxicity (diarrhea, nausea, vomiting) is common and dose-limiting. Bone marrow suppression (leukopenia, anemia) increases infection risk, notably reactivation of CMV and BK virus in transplant patients. It is significantly teratogenic (associated with congenital malformations and increased miscarriage risk), so effective contraception is required in women of childbearing age—this distinguishes it from azathioprine, which is safer in pregnancy.

Mechanism comparison: Unlike azathioprine (which is converted to 6-mercaptopurine and incorporated into DNA/RNA, also affecting purine synthesis but less selectively), mycophenolate offers more lymphocyte-specific immunosuppression with less myelosuppression in many patients, though both drugs are purine synthesis inhibitors and are classic Step 1 comparison points.

High-yield associations: IMPDH inhibitor, blocks de novo (not salvage) purine synthesis, lymphocyte-selective, used in transplant and lupus nephritis, teratogenic, GI and hematologic toxicity.