Crebinostat is a novel and potent HDAC (histone deacetylase) inhibitor with anticancer and neuroprotective effects. HDACs 1-3 and 6 are inhibited by it, with IC50 values of 0.7 nM, 1.0 nM, 2.0 nM, and 9.3 nM, respectively.
Physicochemical Properties
| Molecular Formula | C20H23N3O3 |
| Molecular Weight | 353.414924860001 |
| Exact Mass | 353.173 |
| Elemental Analysis | C, 67.97; H, 6.56; N, 11.89; O, 13.58 |
| CAS # | 1092061-61-4 |
| Related CAS # | 1092061-61-4 |
| PubChem CID | 25118059 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Index of Refraction | 1.583 |
| LogP | 2.87 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 26 |
| Complexity | 453 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(CCCCCC(NO)=O)N/N=C\C1C=CC(=CC=1)C1C=CC=CC=1 |
| InChi Key | AEIVDBATQVVQFS-RCCKNPSSSA-N |
| InChi Code | InChI=1S/C20H23N3O3/c24-19(9-5-2-6-10-20(25)23-26)22-21-15-16-11-13-18(14-12-16)17-7-3-1-4-8-17/h1,3-4,7-8,11-15,26H,2,5-6,9-10H2,(H,22,24)(H,23,25)/b21-15+ |
| Chemical Name | N'-hydroxy-N-[(E)-(4-phenylphenyl)methylideneamino]heptanediamide |
| Synonyms | Crebinostat |
| 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 |
| 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 = 0.7 nM); HDAC2 (IC50 = 1 nM); HDAC3 (IC50 = 2 nM); HDAC6 (IC50 = 9.3 nM) | |
| ln Vitro |
Crebinostat (1 μM; 24 h) induces acetylation of AcH4K12 and AcH3K9 in mouse primary neuronal cells[1]. Crebinostat (1 μM; 24 h) upregulates Bdnf and Hspa1b (Hsp70) mRNA expression while downregulating Mapt mRNA expression in mouse primary cultured neurons[1]. Crebinostat (1 μM; 24 h) raises synapsin and histone acetylation. In primary cultured neurons, I punctae are found along dendrites[1]. |
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| ln Vivo |
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| Cell Assay |
Cell Line: Mouse primary neuronal cells (dissociated from E17 embryonic mouse forebrain) Concentration: 1 μM Incubation Time: 24 h Result: Induced robust acetylation of AcH4K12 and AcH3K9 in a dose dependent manner with EC50s of 0.29 μM and 0.18 μM. |
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| Animal Protocol |
Male C57BL/6J mice (9-10 weeks)[1] 25 mg/kg IP; alternate daily between left and right sides of the abdomen, for 10 days |
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| References |
[1]. Crebinostat: a novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity. Neuropharmacology. 2013 Jan;64:81-96. |
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| Additional Infomation | N'-hydroxy-N-[(4-phenylphenyl)methylideneamino]heptanediamide is a member of biphenyls. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~282.96 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.07 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 (7.07 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8296 mL | 14.1479 mL | 28.2957 mL | |
| 5 mM | 0.5659 mL | 2.8296 mL | 5.6591 mL | |
| 10 mM | 0.2830 mL | 1.4148 mL | 2.8296 mL |