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].

Anticancer agent 82 (compound 4e) (0-10 mM; 72 h) exhibits an IC50 value of 44 nM against HT-1080 fibrosarcoma, surpassing FiVe1 (IC50 = 1.6 μM, HT-1080) [1]. It induces phosphorylation of VIM at Ser56 (0.1 μM; 24 h) [1] and demonstrates poor stability, with 0.0% remaining after 60 minutes in mouse liver microsomes (100 μM; sampled at 0, 5, 15, 30, 45, and 60 min) [1]. Cell viability assays show inhibition of HT-1080, RD, and MCF-7 cells, with IC50 values of 44 nM, 61 nM, and 49 nM, respectively (0-10 mM; 72 hours) [1].

Anticancer agent 82 (compound 4e), administered orally at a dose of 10 mg/kg, demonstrated superior oral pharmacokinetic properties compared to Five1 [1]. Detailed pharmacokinetic analysis in mice [1] revealed that when given orally, compound 4e resulted in an area under the curve (AUC) from time zero to the last measurable concentration (0-last) of 371.33 ng·h/mL, an AUC from time zero to infinity (0-inf) of 534.33 ng·h/mL, a half-life (T 1/2) of 4.68 hours, time to maximum concentration (T max) of 0.67 hours, time of the last measurable concentration (T last) of 8 hours, and a maximum concentration (C max) of 154.67 ng/mL. In comparison, Five1, also given orally but at a 25 mg/kg dose, showed an AUC (0-last) of 309.78 ng·h/mL, AUC (0-inf) of 339.21 ng·h/mL, T 1/2 of 4.57 hours, T max of 0.5 hours, T last of 18 hours, and C max of 110.43 ng/mL.