HMN-214 (IVX-214) is a potent PLK1 inhibitor with an average IC50 of 0.12 μM.

PLK1:0.12 μM.

HMN-214, an oral prodrug of HMN-176, exhibits superior oral bioavailability. In nude mouse models carrying multi-drug resistant KB-A.1 cells, HMN-214 (10 mg/kg-20 mg/kg) significantly inhibits the expression of MDR1 mRNA. Additionally, in mouse xenograft models of PC-3, A549, and WiDr cells, HMN-214 (10 mg/kg-20 mg/kg) effectively suppresses tumor growth.

HMN-214 is an orally administered prodrug that quickly converts to HMN-176, with limited in vitro data available. The active metabolite, HMN-176, demonstrates effective and broad-spectrum antitumor activity against a variety of cancer cell lines including HeLa, PC-3, DU-145, MIAPaCa-2, U937, MCF-7, A549, and WiDr, with an average IC50 value of 118 nM. HMN-176 at concentrations ranging from 250 nM to 2.5 μM inhibits mitotic spindle assembly and at 2.5 μM also impedes microtubule formation from the centrosome. These outcomes suggest that HMN-176's anticancer activity is, in part, mediated by disrupting centrosome-driven microtubule (MT) assembly during mitosis. Additionally, at 2.5 μM, HMN-176 delays the formation of the proper spindle assembly checkpoint in human RPE1 and CFPAC-1 cells. By disrupting the interaction between the NF-Y transcription factor and the MDR1 promoter, HMN-176 (3 μM) downregulates the expression of the multidrug resistance gene (MDR1). In HeLa cells, HMN-176 (3 μM) blocks cell cycle progression at the G2/M phase. HMN-176 also exhibits cytotoxic effects on both human and murine cell lines resistant to various treatments, including P388/CDDP, P388/VCR, K2/CDDP, and K2/VP-16, with IC50 values ranging from 143 nM to 265 nM.

Cells are seeded into a 96-well microplate at a density of 3 × 103–1 × 104 cells/well. Dilutions of HMN-214 or HMN-176 are added the next day and the plate is incubated for 72 hours. The inhibition of growth is measured by the MTT assay and IC50 values are then obtained.(Only for Reference)