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Dacinostat (formerly LAQ824; NVP-LAQ824) is a novel, potent and hydroxamate-based inhibitor of histone deacetylase (HDAC) with potential anticancer activity. It exhibits strong anti-proliferative activity in vitro against a variety of cancer cell lines, including H23 and H460 cell lines, and inhibits HDAC with an IC50 of 32 nM.
Physicochemical Properties
| Molecular Formula | C22H25N3O3 | |
| Molecular Weight | 379.46 | |
| Exact Mass | 379.189 | |
| Elemental Analysis | C, 69.64; H, 6.64; N, 11.07; O, 12.65 | |
| CAS # | 404951-53-7 | |
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| PubChem CID | 6445533 | |
| Appearance | Light yellow to yellow solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Index of Refraction | 1.693 | |
| LogP | 3.41 | |
| Hydrogen Bond Donor Count | 4 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 9 | |
| Heavy Atom Count | 28 | |
| Complexity | 505 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | O([H])C([H])([H])C([H])([H])N(C([H])([H])C1C([H])=C([H])C(/C(/[H])=C(\[H])/C(N([H])O[H])=O)=C([H])C=1[H])C([H])([H])C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 |
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| InChi Key | BWDQBBCUWLSASG-MDZDMXLPSA-N | |
| InChi Code | InChI=1S/C22H25N3O3/c26-14-13-25(12-11-19-15-23-21-4-2-1-3-20(19)21)16-18-7-5-17(6-8-18)9-10-22(27)24-28/h1-10,15,23,26,28H,11-14,16H2,(H,24,27)/b10-9+ | |
| Chemical Name | (E)-N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]prop-2-enamide | |
| Synonyms | NVP-LAQ824; NVP-LAQ-824; NVP LAQ824; LAQ 824; LAQ824; LAQ-824; Dacinostat | |
| 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 | HDAC1 ( IC50 = 9 nM ); HDAC ( IC50 = 32 nM ) | |
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| ln Vivo |
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| Enzyme Assay | Using the Q Sepharose Fast Flow column in ion exchange chromatography, HDAC enzymes are partially isolated from H1299 cell lysate. By using cdk2 polyclonal antibody or cdk1/cdc2 monoclonal antibody for immunoprecipitation, 500 mg of total cell lysate is used to extract enzyme complexes. Re-suspended immunoprecipitates are mixed with 1 μg of pRb recombinant protein substrate (cdk2) or 10 mL of H1 histone mixture containing 20 μg of substrate (cdc2) in kinase buffer (50 mM Hepes, pH 8, 10 mM MgCl2, 2.5 mM EDTA, 1 mM dithiothreitol, 20 mM ATP, 10 mM β-glycerophosphate, 0.1 mM NaVO4, 1 mM sodium fluoride, 50 mM ATP, 10 μCi of [γ-32P]ATP). Electrophoresis is used to separate phosphorylated Rb and H1 histones, and a PhosphorImager is used to quantify the results. | |
| Cell Assay | The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfonyl)-2H-tetrazolium assay is a published procedure that is adapted to measure cell proliferation. The cells are cultivated in RPMI 1640 with 10% FBS after being seeded in 12-well dishes. TSA at different concentrations—up to 1,000 ng/mL—is present during cell culture. Trypan blue dye exclusion is used to measure the viable cell counts in a Nesbauer-type hemocytometer at 0 hours, 24 hours, and 48 hours in order to investigate the growth inhibition caused by TSA. To the RPMI 1640 medium, the same volume of ethanol is added as in the control experiment. Every experiment is carried out in triplicate and is repeated three times. Each experimental well has its average background value (treatment with medium alone) deducted; values are averaged for each compound dilution in triplicate. The percentage of growth is computed using the following formulas: If X>T0, then %Growth=(X-T0)/(GC-T0)*100; if X0, then %Growth=(X-T0)/T0*100. where X is the average value of compound-treated cells (in triplicate)-background, GC is the average value of untreated cells (in triplicate) − background, and T0 is the average value of T0 − background. In order to predict the concentration of compounds at 50% inhibition, the "% Growth" is plotted against compound concentration and used to calculate the IC50 using linear regression techniques between data points. | |
| Animal Protocol |
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| References |
[1]. Selective growth inhibition of tumor cells by a novel histone deacetylase inhibitor, NVP-LAQ824. Cancer Res. 2004 Jan 15;64(2):689-95. [2]. Conformational refinement of hydroxamate-based histone deacetylase inhibitors and exploration of 3-piperidin-3-ylindole analogues of dacinostat (LAQ824). J Med Chem. 2010 Apr 8;53(7):2952-63. [3]. Deacetylase inhibitors modulate proliferation and self-renewal properties of leukemic stem and progenitor cells. Cell Cycle. 2012 Sep 1;11(17):3219-26. |
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| Additional Infomation |
N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide is a member of tryptamines. Dacinostat is a novel histone deacetylase inhibitor. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.59 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 (6.59 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 (6.59 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: 1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6353 mL | 13.1766 mL | 26.3532 mL | |
| 5 mM | 0.5271 mL | 2.6353 mL | 5.2706 mL | |
| 10 mM | 0.2635 mL | 1.3177 mL | 2.6353 mL |