Ispinesib

Ispinesib, also known as SB-715992, is a small-molecule inhibitor of kinesin spindle protein (KSP), a motor protein essential for proper assembly of the mitotic spindle. By inhibiting KSP (KIF11), ispinesib blocks centrosome separation and formation of a bipolar spindle, resulting in mitotic arrest at metaphase and subsequent apoptotic cell death in dividing cells.

The drug was investigated as an anticancer agent in multiple phase I and II clinical trials across various solid tumors, including breast cancer, non-small cell lung cancer, and ovarian cancer. In these trials, some patients showed tumor shrinkage or disease stabilization, but overall response rates were modest, and several studies reported dose-limiting toxicities. The most common adverse effects included neutropenia, fatigue, nausea, diarrhea, constipation, and alopecia, with laboratory abnormalities in blood counts.

Due to limited efficacy and tolerability concerns across trials, ispinesib did not advance to regulatory approval and development for cancer indications has not resulted in an approved therapy. Research into KSP inhibitors continues as a broader approach to disrupt mitosis in cancer cells, though ispinesib-specific development has slowed or ceased in favor of other agents or targets.