Taltobulin : Oncolytic drug Prop INN tubulin polymerization inhibitor antimitotic drug

Antimicrotubule agents are among the most effective drugs for the treatment of breast, ovarian and other forms of cancer. Two classes of antimicrotubule drugs are commonly used: the taxanes, which accelerate tubulin polymerization by stabilizing assembled microtubules and obstructing depolymerization, and the Vinca alkaloids, which bind to the tubulin α/β-heterodimer, block the formation of normal microtubules and lead to the depolymerization of microtubules and/or the formation of abnormal tubulin polymers. While these drugs inhibit tumor progression, their cytotoxic effects on rapidly proliferating normal tissues and other significant side effects are limiting factors. In addition, inherent resistance to antimicrotubule agents is encountered in many tumor types, or acquired resistance may occur during multiple cycles of therapy. Thus, there is great interest in and an unmet need for identifying novel antimicrotubule drugs. Taltobulin (HTI-286, SPA-110) is a novel antimitotic agent that inhibits the polymerization of tubulin, disrupts microtubule dynamics in cells and induces mitotic arrest and apoptosis. Relative to the antimicrotubule drugs in use, taltobulin exhibits significantly less interaction with the multidrug resistance protein (P-glycoprotein) and is effective in inhibiting human tumor xenografts in nude mouse models where paclitaxel and vincristine are ineffective. Taltobulin administered i.v. or p.o. in saline inhibits the growth of numerous human tumors without the side effects associated with formulations. Taltobulin is in clinical development.