HMN-176 is a stilbene derivative which inhibits mitosis, interfering with polo-like kinase-1 (plk1), without significant effect on tubulin polymerization. 

PLK1^[5]

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

382.43

C₂₀H₁₈N₂O₄S

173529-10-7

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 30 mg/mL (78.45 mM)

* “≥” means soluble, but saturation unknown.

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

• [1]. DiMaio MA, et al. The small organic compound HMN-176 delays satisfaction of the spindle assembly checkpoint by inhibiting centrosome-dependent microtubule nucleation. Mol Cancer Ther. 2009 Mar;8(3):592-601.

  [2]. Medina-Gundrum L, et al. Investigation of HMN-176 anticancer activity in human tumor specimens in vitro and the effects of HMN-176 on differential gene expression. Invest New Drugs. 2005 Jan;23(1):3-9.

  [3]. Takagi M, et al. In vivo antitumor activity of a novel sulfonamide, HMN-214, against human tumor xenografts in mice and the spectrum of cytotoxicity of its active metabolite, HMN-176. Invest New Drugs. 2003 Nov;21(4):387-99.

  [4]. Tanaka H, et al. HMN-176, an active metabolite of the synthetic antitumor agent HMN-214, restores chemosensitivity to multidrug-resistant cells by targeting the transcription factor NF-Y. Cancer Res. 2003 Oct 15;63(20):6942-7.

  [5]. Garland LL, et al. A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. Clin Cancer Res. 2006 Sep 1;12(17):5182-9.

Cells to be tested are seeded into a 96-well microplate at a density of 3 ×10³-1×10⁴ cells/well. Drugs are added the next day and the plate is incubated for 72 h at 37 °C in a humidified incubator (5% CO₂, 95% air). The inhibition of growth is measuredby the MTT assay, and the concentration required to produce 50% inhibition of growth (IC₅₀) calculated by the Scansoft 96 software program. The IC₅₀ values for HMN-176 andreference agents are presented. Briefly, for each compound the mean IC₅₀ value for all cell lines tested is calculated and the difference between the individual IC₅₀ values and the mean IC₅₀ value (log10) displayed by a bar projecting to the right or left of the mean. The resistance index is calculated as (IC₅₀ value for drug-resistant cell line)/(IC₅₀ for parent cell line).

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

¹⁴C-HMN-214 and ¹⁴C-HMN176 are p.o. to male SD rats at doses of 33 (equivalent to 30 mg/kg of HMN-176) and 30 mg/kg, respectively. Blood samples are collected at designated times and plasma levels of radioactivity determined with a liquid-scintillation counter. In addition, unlabeled HMN-214 (33 mg/kg) is administered to male rats and plasma concentrations of HMN-214 and HMN-176 are determined by high performance liquid chromatography.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. DiMaio MA, et al. The small organic compound HMN-176 delays satisfaction of the spindle assembly checkpoint by inhibiting centrosome-dependent microtubule nucleation. Mol Cancer Ther. 2009 Mar;8(3):592-601.

  [2]. Medina-Gundrum L, et al. Investigation of HMN-176 anticancer activity in human tumor specimens in vitro and the effects of HMN-176 on differential gene expression. Invest New Drugs. 2005 Jan;23(1):3-9.

  [3]. Takagi M, et al. In vivo antitumor activity of a novel sulfonamide, HMN-214, against human tumor xenografts in mice and the spectrum of cytotoxicity of its active metabolite, HMN-176. Invest New Drugs. 2003 Nov;21(4):387-99.

  [4]. Tanaka H, et al. HMN-176, an active metabolite of the synthetic antitumor agent HMN-214, restores chemosensitivity to multidrug-resistant cells by targeting the transcription factor NF-Y. Cancer Res. 2003 Oct 15;63(20):6942-7.

  [5]. Garland LL, et al. A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. Clin Cancer Res. 2006 Sep 1;12(17):5182-9.