HMN-214

• CAT Number: I002261
• CAS Number: 173529-46-9
• Molecular Formula: C22H20N2O5S
• Molecular Weight: 424.47
• Purity: ≥95%
• Target: PLK
• Solubility: 10 mM in DMSO
• Storage: 3 years -20C powder
• IC50: 0.12 μM

HMN-214(IVX214) is a potent PLK1 inhibitor an average IC50 of 0.12 μM.IC50 Value: 0.12 μMTarget: PLK1in vitro: 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.

Reference

1: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. Garland LL, Taylor C, Pilkington DL, Cohen JL, Von Hoff DD.Clin Cancer Res. 2006 Sep 1;12(17):5182-9. PMID: 16951237 Free Article2: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. Takagi M, Honmura T, Watanabe S, Yamaguchi R, Nogawa M, Nishimura I, Katoh F, Matsuda M, Hidaka H.Invest New Drugs. 2003 Nov;21(4):387-99. PMID: 14586206 3: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. Tanaka H, Ohshima N, Ikenoya M, Komori K, Katoh F, Hidaka H.Cancer Res. 2003 Oct 15;63(20):6942-7. PMID: 14583495 Free Article