RAD001 (Everolimus) is an orally-bioavailable, semi-synthetic mTOR inhibitor with immunosuppressive activity. It has an IC50 against FKBP12 (FK506-binding protein 12) of 1.8-2.6 nM. Moreover, in an IL-6-dependent hybridoma clone, growth factor-stimulated cell proliferation was measured at an IC50 of 0.2-1.4 nM. Immunosuppressant activity was measured in a mouse lymphocyte reaction model and was determined to be 0.2-1.6 nM. In a Human T-cell clone model, its IC50 was 0.05-0.17 nM. (1)

Everolimus binds to FKBP12, thus forming a complex that inhibits mTOR activity and concomitantly reduces downstream markers such as S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E-binding protein (4EBP). (2)

Everolimus has been used in combination with agents such as Letrozole to inhibit proliferation and trigger apoptosis, which has implications in therapies for hormone-dependent breast cancers. (3)