Cytotoxic agents mycophenolate mofetil

Azathioprine, cyclophosphamide, methotrexate, leflunomide Lymphocyte-specific cytotoxic agents Mycophenolate mofetil... 

Unlike these nonspecific agents, mycophenolate mofetil (6.4) tends to be a lymphocyte-specific cytotoxic agent. Mycophenolate mofetil is a semisynthetic derivative of mycophe-nolic acid, isolated from the mold Penicillium glaucum. It inhibits both T and B lymphocyte action. Since it inhibits the enzyme inosine monophosphate dehydrogenase, which catalyses purine synthesis in lymphocytes, this agent has a more specific effect on lymphocytes than on other cell types. Mizoribine (6.5) is a closely related drug which inhibits nucleotide synthesis, preferentially in lymphocytes. 

FK-506 (37) interferes with IL-2 synthesis and release and has a cyclosporin-like profile, but is considerably more potent in vitro. IC q values are approximately 100-fold lower. This neutral macroHde suppresses the mixed lymphocyte reaction T-ceU proliferation generation of cytotoxic T-ceUs production of T-ceU derived soluble mediators, such as IL-2, IL-3, and y-IFN and IL-2 receptor expression (83). StmcturaHy, FK-506 is similar to sirolimus. Mycophenolate mofetil (33), brequinar (34), and deoxyspergualin are in various phases of clinical evaluation. Identification of therapeutic efficacy and safety are important factors in the deterrnination of their utiUty as immunosuppressive agents. 

Cytotoxic agents which are exclusively used to achieve immunosuppression are azathioprine and mycophenolate mofetil, although their over all mechanism of action is similar to that of the antitumor dmgs, i.e. inhibition of lymphocyte proliferation after antigen exposure. 

Mycophenolic acid (MPA) was isolated from cultures of Penicillium spp. in 1896 and was purified in 1913. Initially the compound was studied for its antifungal and antibacterial effects and later for its antitumor effects. Many years later, its immunosuppressive activities were recognized and after further developmental work, an ester prodrug mycophenolate mofetil was developed, which was approved by the United States Food and Drug Administration for the prevention of acute renal allograft rejection in 1995 and for heart transplant recipients in 1998. Mycophenolate mofetil is a cytotoxic agent now used for immunosuppressive therapy and is the mofetil ester of MPA, which is the active immunosuppressive agent. 

Mycophenolate mofetil is a functionally selective cytotoxic agent for B and T lymphocytes, where it blocks the production of guanosine nucleotides required for DNA synthesis. For purine biosynthesis, B and T lymphocytes rely on de novo synthesis rather than on the salvage pathway. Lymphocytes have little or no salvage pathway as opposed to other blood marrow elements and parenchymal cells that... 

Mycophenolate mofetil is used for tissue transplantation in combination with tacrolimus or cyclosporine or sirolimus plus glucocorticoids. It is used more than any other cytotoxic drug either at the time of the transplant or following the initiation of acute rejection. Mycophenolate mofetil is a prophylactic agent and cannot be used for chronic rejection or ongoing acute rejection. 

Mycil chlorphenesin tolnafitate. mycophenolate mofetil [usan] (CellCept ) is converted in vivo to n cophenolic add, which has antimetabolite cytotoxic properties. It shows experimental activity as an ANTICANCER and ANTIVIRAL AGENT. It may be clinically useful in treating psoriasis and as an ANTU.EISHMANIAL. It shows IMMUNOSUPPRESSANT properties, and is used in the prophylaxis of acute kidney rejection, mycophenolic acid [ban, inn, usan] is usually... 

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