Molecular Formula | C20H18N2O4S |
Molar Mass | 382.43 |
Density | 1.24±0.1 g/cm3(Predicted) |
Boling Point | 632.9±65.0 °C(Predicted) |
Solubility | DMSO: ≥ 30 mg/mL |
pKa | 8.07±0.10(Predicted) |
Storage Condition | under inert gas (nitrogen or Argon) at 2-8°C |
In vitro study | 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. 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. HMN-176 shows potent cytotoxicity, with a mean IC 50 value of 118 nM. HMN-176 displays similar cytotoxicity against tumors with various characteristics from different organs. 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. |
In vivo study | 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. 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. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.615 ml | 13.074 ml | 26.148 ml |
5 mM | 0.523 ml | 2.615 ml | 5.23 ml |
10 mM | 0.261 ml | 1.307 ml | 2.615 ml |
5 mM | 0.052 ml | 0.261 ml | 0.523 ml |
biological activity | HMN-176 is an active metabolite of HMN-214 and HMN-214 has potent antitumor activity in a mouse xenograft model. HMN-176 can effectively inhibit PLK-1 by interfering with its normal subcellular distribution in the centrosome and along the cytoskeletal structure. |
Target | PKL1 |
in vitro study | HMN-176 (2.5 μm). The effect of HMN-176. HMN-176 (2.5, 0.25, and 0.025 μm). 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. HMN-176 shows potent cytotoxicity, with a mean IC 50 value of 118 nM. HMN-176 displays similar cytotoxicity against tumors with various characteristics from different organs. 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. |
in vivo studies | HMN-176 preventions spinning assembly., aster formation. Oocytes treated with 0.25 μm HMN-176 undergoes GVBD, but asters or spindles failures form, even after prolonged periods. 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. |