4SC-205

4SC-205 is an oral small-molecule inhibitor of the human kinesin spindle protein Eg5, which is of crucial importance for proper cell division (mitosis). Mitosis inhibitors, such as taxol, are used as the first-line therapy in numerous cancers. As opposed to taxol, which is neurotoxic, 4SC- 205 does not directly affect microtubules, but only the kinesin Eg5 which is only present during cell division. This compound is in the Phase I AEGIS study in patients with solid tumours or malignant lymphoma in order to evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics. Currently, 4SC-205 is the only oral Eg5 kinesin inhibitor in clinical development.

Eg5 interacts with microtubules, a component of the mitosis mechanism, and mediates the segregation of the two spindle poles resulting in the correct distribution of the chromosomes to the daughter cells. Allosteric inhibition of Eg5 by 4SC- 205 leads to cell cycle arrest in mitosis and subsequent programmed cell death (apoptosis). Mitosis is the fundamental process required for cell division and tissue proliferation. The mitotic spindle apparatus has for decades been a primary target for the development of anti-mitotic drugs such as taxanes and vinca alkaloids, which are broadly used in cancer therapies as single chemotherapeutic agents or in combination. In preclinical tests, 4SC-205 has proven to be a particularly efficacious inhibitor of tumour cell proliferation of various cancer origins, both in vitro and in vivo.