HMN-214 (HMN 214; HMN214), stilbene derivative, is a potent and orally bioactive prodrug of HMN-176, which alters the cellular spatial orientation of Plk1 (polo-like kinase-1). Poly-like kinase-1 (PLK1) is a serine/threonine kinase that controls important mitotic events. HMN-214 tampers with PLK1's subcellular geolocation. The mean IC50 of HMN-176 was 118 nM, indicating strong cytotoxicity. Furthermore, compared to other agents tested, HMN-176 was more cytotoxic toward drug-resistant phenotypes of tumor cells as indicated by its low resistance indices.
Physicochemical Properties
| Molecular Formula | C22H20N2O5S | |
| Molecular Weight | 424.47 | |
| Exact Mass | 424.109 | |
| Elemental Analysis | C, 62.25; H, 4.75; N, 6.60; O, 18.85; S, 7.55 | |
| CAS # | 173529-46-9 | |
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| PubChem CID | 9888590 | |
| Appearance | White to off-white solid powder | |
| Density | 1.2±0.1 g/cm3 | |
| Boiling Point | 663.1±65.0 °C at 760 mmHg | |
| Flash Point | 354.8±34.3 °C | |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C | |
| Index of Refraction | 1.598 | |
| LogP | 1.85 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 5 | |
| Rotatable Bond Count | 6 | |
| Heavy Atom Count | 30 | |
| Complexity | 689 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | S(C1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])[H])(N(C(C([H])([H])[H])=O)C1=C([H])C([H])=C([H])C([H])=C1/C(/[H])=C(\[H])/C1C([H])=C([H])[N+](=C([H])C=1[H])[O-])(=O)=O |
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| InChi Key | OCKHRKSTDPOHEN-BQYQJAHWSA-N | |
| InChi Code | InChI=1S/C22H20N2O5S/c1-17(25)24(30(27,28)21-11-9-20(29-2)10-12-21)22-6-4-3-5-19(22)8-7-18-13-15-23(26)16-14-18/h3-16H,1-2H3/b8-7+ | |
| Chemical Name | N-(4-methoxyphenyl)sulfonyl-N-[2-[(E)-2-(1-oxidopyridin-1-ium-4-yl)ethenyl]phenyl]acetamide | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | PLK1 |
| ln Vitro | HMN-214 is a prodrug of HMN-176. HMN-176 has a mean IC50 of 118 nM and exhibits strong activities against 22 human tumor cell lines[1]. In HeLa cells, HMN-176 (3-300 nM) dose-dependently suppresses luciferase expression regulated by the MDR1 promoter. Additionally, complex formation on the Y-box is dose-dependently suppressed by HMN-176 (30-3000 nM)[3]. In PC3-PSMA cells, HMN-214 (3.3 μM) increases luciferase expression 11-fold over vehicle control when using the 1,4C-1,4Bis polymer and 37-fold when using PEI. In MB49 cells, HMN-214 (≥ 3.3 μM) dramatically suppresses cell proliferation and causes notable morphological changes in the cells[4]. |
| ln Vivo | HMN-214 (33 mg/kg, p.o.) converts to HMN-176 in rats. The aciatic and tibial nerves' action potential amplitude and conduction velocity are unaffected by HMN-214. In mice, HMN-214 (20 mg/kg, p.o.) shows antitumor activity[1]. HMN-214 (10, 20 mg/kg, p.o.) reduces the expression of MDR1 mRNA in tumor-derived KB and KB-A.1 in nude mice[3]. |
| Enzyme Assay | HMN-214 is a potent and orally active prodrug of HMN-176, which alters the cellular spatial orientation of Plk1. |
| Cell Assay | The density of cells is seeded at 3 × 103–1 × 104 cells/well in a 96-well microplate. The plate is incubated for 72 hours after dilutions of HMN-214 or HMN-176 are added the following day. Following the MTT assay, IC50 values are obtained, which indicate the degree of growth inhibition. |
| Animal Protocol | Using an agate pestle, progressively add 0.5% methylcellulose 4000 solution to the ground HMN-214 to create a 3 mg/mL suspension. To get suspensions with the right concentration, this is further diluted with methylcellulose 4000 solution. By s.c. transplantation into naked mice, tumor tissue is grown beforehand. The resulting tumors are excised, cut into 8 mm3 cubic fragments, and then surgically transplanted subcutaneously using a trocar into the right axillary region of naked mice. On day 1, oral administration of HMN-214 is initiated once the tumor's theoretical volume has reached approximately 145 mm3. |
| References |
[1]. 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. [2]. 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. Clin Cancer Res. 2006 Sep 1;12(17):5182-9. [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. Cancer Res. 2003 Oct 15;63(20):6942-7. [4]. Kinome-level screening identifies inhibition of polo-like kinase-1 (PLK1) as a target for enhancing non-viral transgene expression. J Control Release. 2015 Apr 28;204:20-9. |
| Additional Infomation | N-(4-methoxyphenyl)sulfonyl-N-[2-[2-(1-oxido-4-pyridin-1-iumyl)ethenyl]phenyl]acetamide is a sulfonamide. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.62 mg/mL (1.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.2 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.62 mg/mL (1.46 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.2 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.62 mg/mL (1.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.2 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 0.5% methylcellulose: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3559 mL | 11.7794 mL | 23.5588 mL | |
| 5 mM | 0.4712 mL | 2.3559 mL | 4.7118 mL | |
| 10 mM | 0.2356 mL | 1.1779 mL | 2.3559 mL |