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CAS No. 173529-46-9
HMN-214 is a prodrug of HMN-176, which alters the cellular spatial orientation of Plk1.
Selleck's HMN-214 has been cited by 5 publications
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Intracellular trafficking of plasmid DNA in the presence and absence of PLK1 inhibitors. PC3-PSMA cells were transfected with polyplexes of PEI:fluorescein (green)-labeled plasmid DNA at a weight ratio of 1:4. Cells treated with A) vehicle control (DMSO) and B) 25 nM BI 2536 are shown 48 h after co-treatment with polyplexes. Cells treated with C) vehicle control (DMSO) and D) HMN-214 are shown 24 h after co-treatment with polyplexes. Scale bar = 20 μm. Blue signal indicates DAPI-stained nuclei, and white arrows indicate sequestration of plasmid DNA in the perinuclear recycling compartment (PNRC). Red arrows indicate altered plasmid DNA localization following treatment with PLK1 inhibitors. Images are representative of three independent experiments (N = 3). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
J Control Release, 2015, 204:20-29.. HMN-214 purchased from Selleck.
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|Description||HMN-214 is a prodrug of HMN-176, which alters the cellular spatial orientation of Plk1.|
HMN-214 is an oral prodrug that is rapidly converted to HMN-176. The in vitro data of HMN-214 are scarce. However, HMN-176, active metabolite of HMN-214, shows potent and broad-spectrumanti-tumor activity against various cancer cells, including HeLa, PC-3, DU-145, MIAPaCa-2, U937, MCF-7, A549, and WiDr, with a mean IC50 value of 118 nM. HMN-176 is also cytotoxic to drug-resistant human and murine cell lines, including P388/CDDP, P388/VCR, K2/CDDP, and K2/VP-16, with IC50 values ranging from 143 nM–265 nM. In HeLa cells, HMN-176 (3 μM) blocks cell cycle at G2/M phase.  In Doxorubicin-resistant K2/ARS cells, HMN-176 inhibits cell growth with an IC50 value of 2 μM. HMN-176 (3 μM) down-regulates the expression of the multidrug resistance gene (MDR1), due to the disturbance of NF-Y transcription factor binding to the MDR1 promoter.  In human RPE1 and CFPAC-1 cells, HMN-176 (2.5 μM) delays satisfaction of the spindle assembly checkpoint. HMN-176 (250 nM–2.5 μM) inhibits meiotic spindle assembly and aster formationin Spisula oocytes. HMN-176 (2.5 μM) also inhibits aster microtubule formation from human centrosomes. These results indicate that the anti-tumor activity of HMN-176 is at least partially via disrupting centrosome-mediated MT assembly during mitosis. 
|In vivo||HMN-214 is an oral pro-drug of HMN-176 with improved oral absorption. HMN-214 (30 mg/kg) triggers no obvious neurotoxicity in mice. In mouse xenograft model of PC-3, A549, and WiDr cells, HMN-214 (10 mg/kg–20 mg/kg) inhibits tumor growth.  In nude mice model bearing multidrug-resistant KB-A.1 cells, HMN-214 (10 mg/kg–20 mg/kg) significantly suppresses MDR1 mRNA expression. |
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