Ixabepilone (Mechanism of Action)

In this article, we will discuss Ixabepilone (Mechanism of Action). So, let’s get started.

Mechanism of Action

Ixabepilone is a semi-synthetic analog of epothilone B. Ixabepilone binds directly
to β-tubulin subunits on microtubules, leading to suppression of microtubule dynamics.
Ixabepilone suppresses the dynamic instability of αβ-II and αβ-III microtubules.

Ixabepilone possesses low in vitro susceptibility to multiple tumor resistance mechanisms including efflux transporters, such as MRP-1 and P-glycoprotein (P-gp). Ixabepilone blocks cells in the mitotic phase of the cell division cycle, leading to cell death.

Pharmacodynamics

In cancer patients, ixabepilone has a plasma concentration-dependent effect on
tubulin dynamics in peripheral blood mononuclear cells that is observed as the formation of microtubule bundles. Ixabepilone has antitumor activity in vivo against multiple
human tumor xenografts, including drug-resistant types that overexpress P-gp, MRP-1, and βIII tubulin isoforms, or harbor tubulin mutations. Ixabepilone is active in xenografts that are resistant to multiple agents including taxanes, anthracyclines, and vinca alkaloids.

Ixabepilone demonstrated synergistic antitumor activity in combination with capecitabine in vivo. In addition to direct antitumor activity, ixabepilone has antiangiogenic activity.

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