"目录号: HY-13647
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HMN-176 是二苯基乙烯的衍生物，能够抑制有丝分裂，但对微管蛋白的聚合影响不大。
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生物活性
Description
HMN-176?is a stilbene derivative which inhibits mitosis without significant effect on tubulin polymerization.?
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 IC50value 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
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 μM 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.