HMN-176
目录号 : GC19192
HMN-176 是一种二苯乙烯衍生物，可抑制有丝分裂，干扰 polo 样激酶 1 (plk1)，对微管蛋白聚合没有显着影响。
Cas No.:173529-10-7
Sample solution is provided at 25 µL, 10mM.
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HMN-176 is a stilbene derivative which inhibits mitosis, interfering with polo-like kinase-1 (plk1), without significant effect on tubulin polymerization.
HMN-176 (2.5 uM) 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 uM) inhibits aster formation in a concentration dependent manner[1]. HMN-176 (0.1, 1.0, or 10.0 ug/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 ug/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 uM HMN-176 suppresses the expression of MDR1 mRNA by 56%. HMN-176 has no significant effect on the residual promoter activity[4].
HMN-176 prevents spindle assembly and meiosis in Spisula oocytes by inhibiting centrosome-dependent MT nucleation, i.e., aster formation. Oocytes treated with 0.25 uM HMN-176 undergoes GVBD, but asters or spindles fails to form, even after prolonged periods[1]. 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].
References:
[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.
Cell experiment: | 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). |
Animal experiment: | 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. |
References: [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. | |
| Cas No. | 173529-10-7 | SDF | |
| Canonical SMILES | O=S(C1=CC=C(OC)C=C1)(NC2=CC=CC=C2/C=C/C3=CC=N(C=C3)=O)=O | ||
| 分子式 | C20H18N2O4S | 分子量 | 382.43 |
| 溶解度 | DMSO : ≥ 30 mg/mL (78.45 mM) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6149 mL | 13.0743 mL | 26.1486 mL |
| 5 mM | 0.523 mL | 2.6149 mL | 5.2297 mL |
| 10 mM | 0.2615 mL | 1.3074 mL | 2.6149 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet