Drug intelligence / Profile preview

methotrexate + prednisolone + tacrolimus

Development stage
Unknown
Lead developer
Astellas Pharma
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules
Administration
Oral, Intravenous
01

Overview

This is a combination regimen consisting of three immunosuppressive agents—methotrexate, prednisolone, and tacrolimus. Methotrexate is an antimetabolite and antifolate agent that inhibits dihydrofolate reductase, leading to suppression of DNA synthesis and immune cell proliferation. Prednisolone is a synthetic glucocorticoid corticosteroid with potent anti-inflammatory and immunosuppressive properties, acting primarily through glucocorticoid receptor agonism to modulate gene expression and suppress pro-inflammatory cytokines. Tacrolimus is a calcineurin inhibitor that binds FKBP-12 to inhibit calcineurin phosphatase activity, thereby blocking T-cell activation by preventing interleukin-2 transcription. This combination has been studied for the prevention of acute graft-versus-host disease (GVHD) in bone marrow transplantation as well as for refractory autoimmune diseases such as rheumatoid arthritis or necrotizing myopathies[1][3][10]. The regimen aims to provide broad immunosuppression by targeting multiple pathways involved in immune activation.

02

Targets

GR (Glucocorticoid receptor)DHFR (Dihydrofolate reductase)CN (Calcineurin)

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