Drug intelligence / Profile preview

sirolimus + daclizumab + mycophenolate mofetil + corticosteroids

Development stage
Unknown
Lead developer
Roche
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Oral, Intravenous
01

Overview

A four-drug **immunosuppressive regimen** combining sirolimus, daclizumab, mycophenolate mofetil, and corticosteroids, primarily used in organ transplantation to prevent acute rejection. - **Sirolimus** is an mTOR inhibitor that suppresses lymphocyte activation and proliferation. - **Daclizumab** is a monoclonal antibody targeting the interleukin-2 receptor alpha chain (CD25), blocking T-cell activation. - **Mycophenolate mofetil** is an immunosuppressive antimetabolite that inhibits inosine monophosphate dehydrogenase in lymphocytes, thereby blocking purine synthesis and T- and B-cell proliferation. - **Corticosteroids** are anti-inflammatory and immunosuppressive agents that broadly suppress immune response via glucocorticoid receptor agonism and transcriptional regulation of many pro-inflammatory genes. This combination was used in renal and heart transplantation as a calcineurin inhibitor-free regimen to reduce the incidence of graft rejection and limit calcineurin inhibitor-related toxicity. Clinical studies showed increased exposure to mycophenolic acid, variable efficacy, and typical immunosuppression side effects. Daclizumab has been withdrawn from the market.

02

Targets

GR (Glucocorticoid receptor)mTOR (Mammalian target of rapamycin kinase)IMPDH (Inosine-5'-monophosphate dehydrogenase 1)IL2RA (Interleukin-2 receptor alpha subunit)

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