product name HMN-214
Description: HMN-214 is an oral prodrug of HMN-176, which alters the cellular spatial orientation of Plk1. HMN-214 is a stilbene derivative that interferes with the subcellular spatial location of polo-like kinase-1, a serine/threonine kinase that regulates critical mitotic events. HMN-176 showed potent cytotoxicity, with a mean IC50 of 118 nM. In addition, judging by its low resistance indices, HMN-176 was more cytotoxic toward the drug-resistant phenotypes of tumor cells than were the other agents tested.
References: Invest New Drugs. 2003 Nov;21(4):387-99; Cancer Res. 2003 Oct 15;63(20):6942-7.
424.47
Formula
C22H20N2O5S
CAS No.
173529-46-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 12 mg/mL (28.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% methylcellulose: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: Cell Assay: Cells are seeded into a 96-well microplate at a density of 3 × 103–1 × 104 cells/well. Dilutions of HMN-214 or HMN-176 are added the next day and the plate is incubated for 72 hours. The inhibition of growth is measured by the MTT assay and IC50 values are then obtained. |
|---|---|
| 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. |
| Animal model | Male BALB/c nude mice bearing xenografts of PC-3, A549, and WiDr cells |
| Formulation & Dosage | Dissolved in 0.5% methylcellulose; 10, 20 mg/kg; Oral gavage |
| References | Invest New Drugs. 2003 Nov;21(4):387-99; Cancer Res. 2003 Oct 15;63(20):6942-7. |
