folate-epothilone

Folate-epothilone refers to a class of small molecule drug conjugates (SMDCs) designed to target the folate receptor (FR), which is frequently overexpressed in various solid tumors, including ovarian, lung, and breast cancers. These conjugates typically consist of a folic acid targeting ligand covalently linked to an epothilone payload (such as epothilone B or its derivatives). Epothilones are potent microtubule-stabilizing agents that, unlike taxanes, are generally not substrates for the P-glycoprotein (Pgp) efflux pump, allowing them to remain active in multi-drug resistant (MDR) cancer cells. The lead candidate in this category, developed by Endocyte (now part of Novartis), was **EC0489**, which utilized a disulfide-based linker to release the epothilone payload intracellularly upon receptor-mediated endocytosis. While EC0489 demonstrated activity against FR-positive and drug-resistant cell lines and reached Phase 1 clinical trials for refractory solid tumors, its development was eventually discontinued in favor of other folate-targeted assets.

Other names

folate-epothilone B conjugatefolate-targeted epothilone