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Droxinostat (formerly NS-41080) is a novel, potent, selective inhibitor of histone deacetylase (HDAC) with potential anticancer activity. It exhibits >8-fold selectivity over HDAC3 and inhibits HDAC6 and HDAC8 with IC50s of 2.47 μM and 1.46 μM, respectively.
Physicochemical Properties
| Molecular Formula | C11H14CLNO3 | |
| Molecular Weight | 243.69 | |
| Exact Mass | 243.066 | |
| Elemental Analysis | C, 54.22; H, 5.79; Cl, 14.55; N, 5.75; O, 19.70 | |
| CAS # | 99873-43-5 | |
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| PubChem CID | 568416 | |
| Appearance | White to off-white solid powder | |
| Density | 1.252 g/cm3 | |
| LogP | 3.153 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 5 | |
| Heavy Atom Count | 16 | |
| Complexity | 225 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | ClC1C([H])=C([H])C(=C(C([H])([H])[H])C=1[H])OC([H])([H])C([H])([H])C([H])([H])C(N([H])O[H])=O |
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| InChi Key | JHSXDAWGLCZYSM-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C11H14ClNO3/c1-8-7-9(12)4-5-10(8)16-6-2-3-11(14)13-15/h4-5,7,15H,2-3,6H2,1H3,(H,13,14) | |
| Chemical Name | 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide | |
| Synonyms | NS 41080; NS41080; NS-41080 | |
| 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 | HDAC8 ( IC50 = 1.46 μM ); HDAC6 ( IC50 = 2.47 μM ); HDAC3 ( IC50 = 16.9 μM ) | ||
| ln Vitro |
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| ln Vivo |
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| Enzyme Assay | HDAC inhibition is measured using crude nuclear extract from HeLa cells and the CycLex HDACs fluorometric assay, following the manufacturer's instructions (principally HDAC1 and HDAC2). (Treated sample fluorescence intensity / Control sample fluorescence intensity) × 100 represents the relative activity. | ||
| Cell Assay | PPC-1 cells (1 × 104) are seeded in 100 μL of 2.5% FCS-containing medium overnight into 96-well flat-bottomed plates. We add Droxinostat the following day. After adding CH-11 antibody (100 ng/mL), the cells are incubated for 24 hours. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye reduction assay is then used to determine the viability of the cells. | ||
| Animal Protocol |
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| References |
[1]. Cancer Res . 2006 Feb 15;66(4):2367-75. [2]. J Natl Cancer Inst . 2007 May 16;99(10):811-22. [3]. Mol Cancer Ther . 2010 Jan;9(1):246-56. [4]. Mol Cell Biochem . 2010 Sep;342(1-2):133-142. |
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| Additional Infomation | 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide is an aromatic ether. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.26 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 25.0 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: ≥ 2.5 mg/mL (10.26 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 25.0 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: ≥ 2.5 mg/mL (10.26 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1036 mL | 20.5179 mL | 41.0357 mL | |
| 5 mM | 0.8207 mL | 4.1036 mL | 8.2071 mL | |
| 10 mM | 0.4104 mL | 2.0518 mL | 4.1036 mL |