| ln Vitro |
HIT211504993 can efficiently and selectively inhibit HDAC6, with an IC50 value of 0.070 ± 0.002 μM. Its inhibitory efficacy against HDAC6 is 89 times higher than that against HDAC2 and 486 times higher than that against HDAC4[1]. HIT211504993 (48 h) can selectively inhibit the activity of colorectal cancer cells (HCT-8, HCT116) and other tumor cell lines, with IC50 values of 12.483 μM and 18.840 μM, respectively, and has low toxicity to normal intestinal epithelial cells NCM460[1]. HIT211504993 (10-50 μM; 12-48 h) can effectively enhance the acetylation of histone H3 and non-histone α-tubulin in HCT-8 and HCT116 colorectal cancer cells in a concentration- and time-dependent manner[1]. HIT211504993 (20 μM; 24 h) can inhibit the long-term proliferation of HCT-8 and HCT116 colorectal cancer cells, manifested as a reduction in colony formation [1]. HIT211504993 (20 μM; 12-48 h) can induce G1 phase cell cycle arrest in HCT-8 and HCT116 colorectal cancer cells and downregulate the expression of cyclin D, thereby inhibiting cell proliferation [1]. HIT211504993 (20 μM; 12-48 h) induces time-dependent apoptosis in HCT-8 and HCT116 colorectal cancer cells through the mitochondrial intrinsic pathway, manifested as changes in Bcl-2/Bax expression and an increase in Annexin V positive cells [1]. HIT211504993 (60 μM; 6 h) directly binds to HDAC1 and HDAC2 in HCT-8 colorectal cancer cells, enhancing their thermal stability [1]. HIT211504993 (20 μM; 4–24 hours) regulates gene expression in HCT-8 colorectal cancer cells, downregulates MYC and Wnt/β-catenin pathway components, and upregulates p53 and DUSP1, thereby inhibiting tumorigenesis [1].
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| ln Vivo |
HIT211504993 (25-100 mg/kg; intraperitoneal injection; daily; 15 days) inhibited the growth of HCT-8 colorectal cancer xenografts in a dose-dependent manner, reducing tumor volume by 77% at 50 mg/kg, and was well tolerated [1].
|
| Cell Assay |
Cell viability assay [1]
Cell Types: HCT-8, HCT116, NCM460, A2780, A549, MDA-MB-231, HepG2, HeLa, A375 cells Tested Concentrations: 0.5-100 μM Incubation Duration: 48 hours Experimental Results: The IC50 in HCT-8 cells was 12.483 ± 0.92 μM. The IC50 in HCT116 cells was 18.840 ± 0.88 μM. The IC50 in NCM460 cells was 46.043 ± 3.39 μM. The IC50 in A2780 cells was 33.080 ± 3.98 μM. In A549 cells, the IC50 value was 25.967 ± 5.45 μM. In MDA-MB-231 cells, the IC50 value was 10.782 ± 0.76 μM. In HepG2 cells, the IC50 value was 26.680 ± 1.75 μM. In HeLa cells, the IC50 value was 56.557 ± 3.74 μM. In A375 cells, the IC50 value was 20.983 ± 0.48 μM. Western Blot Analysis [1] Cell Types: HCT-8, HCT116 colorectal cancer cells Tested Concentrations: 10, 20, 30, 40, 50 μM Incubation Duration: 12, 24, 36, 48 hours Experimental Results: The levels of acetylated H3 and acetylated α-tubulin were elevated in both cell lines, with the most significant increase at 20 μM concentration. After incubation at 20 μM concentration for 12-48 hours, the levels of acetylated H3 and acetylated α-tubulin in both cell lines increased in a time-dependent manner. Cell cycle analysis [1] Cell Types: HCT-8 and HCT116 colorectal cancer cells Tested Concentrations: 20 μM Incubation Duration: 12, 24, 36, and 48 hours Experimental Results: Induced G1 phase cell cycle arrest in HCT-8 and HCT116 cells. This resulted in a significant time-dependent decrease in cyclin D expression.
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| Animal Protocol |
Animal/Disease Models:BALB/c nude mice (4-6 weeks old, 16-20 g, xenograft model established by subcutaneous injection of HCT-8 cells) [1]
Doses: 25 mg/kg; 50 mg/kg; 100 mg/kg Route of Administration: Intraperitoneal injection; once daily for 15 days Experimental Results: Compared with the solvent control group, the tumor weight of the 25 mg/kg dose group was significantly reduced. Compared with the solvent control group, the tumor volume of the 50 mg/kg dose group was reduced by 77% and the tumor weight was reduced by 68%. The tumor growth inhibition effect of the 100 mg/kg dose group was better than that of the 50 mg/kg dose group. No significant changes in body weight or histological abnormalities of the heart, liver, spleen, kidney or lung were observed at any of the treatment doses. |
| References |
| Molecular Formula |
C23H27CLN2O6S
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|---|---|
| Molecular Weight |
494.99
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
O=C(C1CCC(CN(CC2=CC=CC(Cl)=C2)S(=O)(C3=CC=C4OCCOC4=C3)=O)CC1)NO
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0202 mL | 10.1012 mL | 20.2024 mL | |
| 5 mM | 0.4040 mL | 2.0202 mL | 4.0405 mL | |
| 10 mM | 0.2020 mL | 1.0101 mL | 2.0202 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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