HMN214

HMN-214 is an oral prodrug of HMN-176, a stilbene derivative that interferes with the subcellular spatial location of polo-like kinase-1, a serine/threonine kinase that regulates critical mitotic events. (In Vitro) :HMN-214 is a prodrug of HMN-176. HMN-176 shows potent activities against 22 human tumor cell lines, with a mean IC50s of 118 nM. HMN-176 (3-300 nM) inhibits luciferase expression driven by the MDR1 promoter in a dose dependent manner in HeLa cells. HMN-176 (30-3000 nM) also dose-dependently suppresses complex formation on the Y-box. HMN-214 (3.3 μM) enhances luciferase expression relative to vehicle control with the 1,4C-1,4Bis polymer (11-fold) and PEI (37-fold) in PC3-PSMA cells. HMN-214 (≥ 3.3 μM) significantly reduces cell proliferation, causes considerable changes in cell morphology in MB49 cells. (In Vivo) :HMN-214 (33 mg/kg, p.o.) converts to HMN-176 in rats. HMN-214 has no effect on the conduction velocity and the amplitude of action potentials in the aciatic and tibial nerves. HMN-214 (20 mg/kg, p.o.) exhibits antitumor activity in mice. HMN-214 (10, 20 mg/kg, p.o.) decreases MDR1 mRNA expression in nude mice bearing KB- and KB-A.1.-derived tumors.