Physicochemical Properties
| Molecular Formula | C29H39N5O5 |
| Molecular Weight | 537.650467157364 |
| Exact Mass | 537.295 |
| CAS # | 2482992-54-9 |
| PubChem CID | 162663441 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 3.9 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 39 |
| Complexity | 742 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | NTUCJWZWDDQYER-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C29H39N5O5/c1-19-15-21(16-20(2)27(19)39-14-8-6-7-9-25(35)32-36)28-30-23-17-22(37-4)18-24(38-5)26(23)29(31-28)34-12-10-33(3)11-13-34/h15-18,36H,6-14H2,1-5H3,(H,32,35) |
| Chemical Name | 6-[4-[5,7-dimethoxy-4-(4-methylpiperazin-1-yl)quinazolin-2-yl]-2,6-dimethylphenoxy]-N-hydroxyhexanamide |
| 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
| ln Vitro | In MDA-MB-231 cells, HDAC-IN-36 (compound 23 g) (0–10, 24 hours) demonstrated strong anti-proliferative effect, encouraging the acetylation of α-tubulin and HSP90 [1]. In MDA-MB-231 cells, HDAC-IN-36 (0-10, 24 h) dose-dependently promotes apoptosis, mostly mitochondria-dependent apoptosis [1]. HDAC-IN-36 (0-10, 24 h) dramatically lowers MMP-2 expression, upregulates E-cadherin expression, and inhibits MDA-MB-231 cell migration in a dose-dependent manner [1]. Significant autophagy can be induced by HDAC-IN-36 (0-10, 24 hours), which can also decrease the expression of SQSTM1/p62 and increase the expression of LC3II and Beclin1 [1]. |
| ln Vivo | HDAC-IN-36 (compound 23 g) exhibits strong anti-tumor and anti-metastatic activity and enhances anti-tumor efficacy in vivo (zebrafish tumor xenograft model; 0–5 μg/mL, 3 days) [1]. Pharmacokinetic parameters demonstrated significant improvements with HDAC-IN-36 (beagle, 20 mg/kg, PO, once) [1]. HDAC-IN-36 pharmacokinetic parameters in male beagle dogs [1]. AUC0-t (μg/L*h) 1275.35 ± 70.17 AUC0-∞ ( μg/L*h) 1289.40 ± 88.91 Parameter 23g (20 mg/kg) T1/2 (h) 1.24 ± 0.21 Tmax (h) 0.79 ± 0.33 Cmax (μg/L) 120.36 ± 15.53 |
| Cell Assay |
Cell viability assay Cell Types: MDA-MB-231 cells [1] Tested Concentrations: 0, 2.5, 5, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated good anti-proliferative activity in MDA-MB-231 cells, IC50 is 1.32 ±0.13 μM, increases the acetylation level of intracellular proteins and promotes the acetylation of α-tubulin and HSP90. Apoptosis analysis Cell Types: MDA-MB-231 cells [1] Tested Concentrations: 0, 2.5, 5, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Apoptosis was induced in MDA-MB-231 cells in a dose-dependent manner. Autophagy assay Cell Types: MDA-MB-231 cells [1] Tested Concentrations: 0, 2.5, 5, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Remarkable autophagy was induced with increased accumulation of LC3 puncta. Western Blot Analysis Cell Types: MDA-MB-231 cells [1] Tested Concentrations: 0, 2.5, 5, 10μM Incubation Duration: 24 hrs (hours) Experimental Results: Mainly induces mitochondria-dependent apoptosis, upregulates Bax expression and downregulates Bcl-2 expression, It also increases the cleavage of caspase3, caspase8 and caspase9; signif |
| Animal Protocol |
Animal/Disease Models: Zebrafish (MDA-MB-231-derived xenograft model, wild-type AB strain) [1] Doses: 0, 2.5, 5 μg/mL Administration time: 3 days Experimental Results: Inhibition of tumor formation and migration was dose-dependent and improved anti-tumor efficacy in vivo. Animal/Disease Models: Beagle dog (female, 8-10 kg, n = 4) [1] Doses: 20 mg/kg (dissolved in 0.5% carboxymethyl cellulose sodium (CMC-Na) aqueous solution) Route of Administration: po (po (oral gavage)) Primary (pharmacokinetic/PK/PK analysis) Experimental Results: pharmacokinetic/PK/PK parameters were Dramatically improved, with a T1/2 value of 1.24 h. |
| References |
[1]. Design, synthesis and biological evaluation of novel HDAC inhibitors with improved pharmacokinetic profile in breast cancer. Eur J Med Chem. 2020;205:112648. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8599 mL | 9.2997 mL | 18.5995 mL | |
| 5 mM | 0.3720 mL | 1.8599 mL | 3.7199 mL | |
| 10 mM | 0.1860 mL | 0.9300 mL | 1.8599 mL |