five1

FiVe1 is a vimentin binding small molecule that promotes the disintegration and phosphorylation of vimentin in the metaphase, leading to mitotic disasters, polynuclearization, and loss of cancer cell dryness. FiVe1 selectively and irreversibly inhibit the growth of mesenchymal transformed breast cancer cells (FOXC2-HMLER cell, IC50=234nM) and soft tissue sarcomas of different histological subtypes.

ADP-2341 is a soluble analog of FiVe1.

Anticancer agent 82 is a FiVe1 derivative, an orally active and selective anticancer agent. FiVe1 binds type III intermediate filament protein vimentin ( VIM ), to induce hyperphosphorylation of Ser56, resulting selective disruption of mitosis and multinucleation in transformed VIM-expressing mesenchymal cancer cells. Anticancer agent 82 shows better oral bioavailability and pharmacokinetic profiles than FiVe1 [1].