Physicochemical Properties
| Molecular Formula | C22H25N5O2S |
| Molecular Weight | 423.53 |
| CAS # | 2988762-46-3 |
| Appearance | Typically exists as solids at room temperature |
| 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 | HDAC3 (IC50=89 nM); HDAC1 (IC50=730 nM); HDAC6 (IC50>10 μM); HDAC7 (IC50>10 μM); HDAC8 (IC50>10 μM); |
| ln Vitro | HDAC3-IN-4 (compound HQ-30) exhibits potent antiproliferative effects, with IC50 values of 0.09 μM, 0.43 μM, 1.20 μM, 2.94 μM and 0.24 μM for Jurkat (T lymphoma), HCT-116 (colorectal cancer), B16-F10 (melanoma), MCF-7 (breast cancer) and HepG2 (liver cancer) cells, respectively[1]. HDAC3-IN-4 (0.5-8 μM; 48 h) induces apoptosis of B16-F10 cells in a concentration-dependent manner[1]. HDAC3-IN-4 (0.5-4 μM; 48 h) dose-dependently increases the percentage of cell cycle arrested at the G2/M phase and decreases the percentage of cells in the G0/G1 phase in B16-F10 cells[1]. HDAC3-IN-4 (0.5-4 μM; 24 h) leads to a significant upregulation of acetylated-H3 (Ac-H3). HDAC3-IN-4 downregulates/reduces PD-L1 expression via the lysosomal pathway[1]. |
| ln Vivo | HDAC3-IN-4 (compound HQ-30; 25 mg/kg; oral; daily; for 9 days) reduces tumor volume and weight, and inhibits tumor growth[1]. Pharmacokinetic parameters of HDAC3-IN-4 in male Sprague-Dawley rats[1]. 1.19 PK parameters iv administration (2 mg/kg, n = 6) po administration (20 mg/kg, n = 6) AUC0-t (ng/mL·h) 521.85 ± 93.78 2742.08 ± 768.82 AUC0-∞ (ng/mL·h) 529.16 ± 91.38 3032.62 ± 805.03 MRT0 -t (h) 0.52 ± 0.09 3.19 ± 0.84 MRT0-∞ (h) 0.55 ± 0.10 4.48 ± 1.75 t1/2 (h) 0.4 ± 0.10 3.6 ± 1.6 Tmax (h) 0.14 ± 0.08 0.50 ± 0 CL (L/h/kg) 3.87 ± 0.65 7.27 ± 3.10 Vz (L/kg) 2.21 ± 0.64 34.45 ± 12.38 Cmax (ng/mL) 725.25 ± 169.59 1038.18 ± 514.59 F (%) - 57 |
| Cell Assay |
Apoptosis Analysis[1] Cell Types: B16-F10 cells Tested Concentrations: 0.5 μM, 1 μM, 2 μM, 4 μM, and 8 μM Incubation Duration: 48 h Experimental Results: Induced cancer cell apoptosis. Cell Cycle Analysis[1] Cell Types: B16-F10 cells Tested Concentrations: 0.5 μM, 1 μM, 2 μM, 4 μM Incubation Duration: 48 h Experimental Results: Dose-dependently increased the percentage of cell cycle arrest. Western Blot Analysis[1] Cell Types: B16-F10 cells Tested Concentrations: 0.5 μM, 1 μM, 2 μM, 4 μM Incubation Duration: 24 h Experimental Results: Caused significant upregulation of acetylated-H3. |
| Animal Protocol |
Animal/Disease Models: Six weeks old C57BL/6J male mice (6 weeks old) injected B16 cells[1] Doses: 25 mg/kg Route of Administration: p.o.; per day; for 9 days Experimental Results: Decreased the tumor volume and tumor weight with tumor growth inhibitions. |
| References |
[1]. Discovery of Novel HDAC3 Inhibitors with PD-L1 Downregulating/Degrading and Antitumor Immune Effects. J Med Chem. 2024 Jul 20. |
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 | 2.3611 mL | 11.8055 mL | 23.6111 mL | |
| 5 mM | 0.4722 mL | 2.3611 mL | 4.7222 mL | |
| 10 mM | 0.2361 mL | 1.1806 mL | 2.3611 mL |