About Sirolimus

Sirolimus is naturally occurring compound

Sirolimus, the active drug released from the CYPHER^® Stent, is a naturally occurring substance. It is marketed by Wyeth Pharmaceuticals under the name Rapamune. The use of sirolimus in the CYPHER^® Stent is part of an exclusive worldwide agreement Cordis has entered into with Wyeth for the localized delivery of sirolimus in certain fields of use.

Background on sirolimus

Sirolimus was first isolated from a soil microorganism, Streptomyces hygroscopicus , found on Easter Island in 1975. Rapa Nui is the local name for Easter Island, inspiring the compound's well-known common name of rapamycin.

Crystalline sirolimus was purified from fermentation media and found to be active against several strains of yeast and filamentous fungi. The producing streptomycete was also active against some bacteria, leading to the original classification of sirolimus as an anti-fungal antibiotic.

In addition to its antibiotic activity, sirolimus also has powerful anti-proliferative and immunosuppressant properties. Sirolimus was shown to be a novel inhibitor of cellular proliferation, distinct from cyclosporin A in a variety of in vitro and in vivo models. The smooth muscle antiproliferative properties have been characterized in numerous vascular models.

In vivo studies in allograft and angioplasty models have demonstrated the effectiveness of sirolimus in preventing tissue hyperplasia following vascular injury, and have led to its consideration as an agent for the prevention of restenosis.

How sirolimus works

Sirolimus belongs to a category of cytostatic drugs known as cell-cycle inhibitors. These drugs selectively stop cell growth, by blocking cell-cycle progression.

Sirolimus’ cytostatic mechanism of action inhibits cell growth by targeting replicating cells while inhibiting cellular response to pro-inflammatory cytokines. As a cytostatic (vs. cytotoxic) drug, sirolimus stops cell proliferation without killing cells, thereby minimizing the risk of tissue pathology.

Sirolimus exerts its inhibitory effects early (G1 phase), rather than late, in the cell cycle — before DNA replicates and the cell begins to divide. Thus, sirolimus exerts a cytostatic effect, rendering the cell quiescent, but functional.