HMN-176

HMN-176?is a stilbene derivative which inhibits mitosis, interfering with polo-like kinase-1 (plk1), without significant effect on tubulin polymerization.? IC50 & Target: PLK1^[5] In Vitro: HMN-176 (2.5 μM) greatly increases the duration of mitosis in hTERT-RPE1 and CFPAC-1 Cell lines. The effect of HMN-176 on spindle morphology does not appear to be related to effects on microtubule polymerization. HMN-176 (2.5, 0.25, and 0.025 μM) inhibits aster formation in a concentration dependent manner^[1]. HMN-176 (0.1, 1.0, or 10.0 μg/mL) demonstrates inhibitory effects in multiple tumors, with notable activity seen in breast, nonsmall-cell lung, and ovarian cancer specimens. HMN-176 demonstrates activity towards 63% of the breast (5/8), 67% of the non-small cell lung (4/6), and 57% of the ovarian (4/7) tumor specimens treated with 10.0 μg/mL^[2]. HMN-176 shows potent cytotoxicity, with a mean IC₅₀ value of 118 nM. HMN-176 displays similar cytotoxicity against tumors with various characteristics from different organs^[3]. Treatment with 3 μM HMN-176 suppresses the expression of MDR1 mRNA by 56%. HMN-176 has no significant effect on the residual promoter activity^[4]. In Vivo: After p.o. of HMN-214 to male rats, the prodrug is not detected in the plasma, while plasma levels of HMN-176 peaks at 2 h and gradually decreases thereafter^[3].