tcsc0202 HMN-214

HMN-214, an orally bioavailable prodrug of HMN-176, is an inhibitor of polo-like kinase-1 (plk1), with antitumor activity.

IC50 & Target: PLK1^[2][4]

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^[1]. 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^[3]. 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^[4].

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^[1]. HMN-214 (10, 20 mg/kg, p.o.) decreases MDR1 mRNA expression in nude mice bearing KB- and KB-A.1.-derived tumors^[3].