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| 10mg |
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| Targets |
HDAC8-IN-2 targets histone deacetylase 8 (HDAC8), which is a member of the class I HDAC family. By binding to the catalytic site of HDAC8, the compound inhibits its deacetylase activity, leading to increased acetylation of histones and other proteins. This results in changes in gene expression and protein function. The compound shows selectivity for HDAC8 over other HDAC isoforms, making it a valuable tool for studying HDAC8-specific functions.
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| ln Vitro |
Compound 2 (20–40 µM; 0-144 hours; BE(2)–C, SK–N–BE(2), and SH–SY5Y cells) treatment resulted in a concentration-dependent reduction in the number of cells Quantity[2]. Compound 2 (1-naphthohydroxamic acid) at concentrations that grew neurite-like structures that stained positive for neurofilaments and decreased cell density within the range of its in vitro IC50 against HDAC8. 1. In soft tissues, naphthohydroxamic acid inhibits the formation of colonies. Dependence of Agar concentration [2]. Only tubulin became hyperacetylated when 1-naphthalene hydroxamic acid (Compound 2; 0.8 µM, 4 µM, 20 µM, or 100 µM) was applied to either kind of cell (HeLa or HEK293 cells)[1].
In vitro, HDAC8-IN-2 demonstrates potent inhibition of HDAC8 activity, with an IC₅₀ in the low micromolar range. The compound increases the acetylation of histones and other HDAC8 substrates in cultured cells. HDAC8-IN-2 has been shown to inhibit the proliferation of various cancer cell lines and to induce apoptosis in cancer cells. The compound also modulates the expression of genes involved in cell cycle regulation, apoptosis, and differentiation. |
| ln Vivo |
Compound 2 (0–40 mg/kg; intraperitoneal; daily; for 10 days; NMRI Foxn1 nude mice) exhibited dose-limiting toxicities (DLT) that included weight loss and indicators of hepatotoxicity, such as increased liver examination histology and the detection of necrotic regions in plasma liver enzymes. 50 mg/kg of 1-naphthalene hydroxamic acid per day is the highest dose that can be tolerated. Neither blood parameters nor body weight are significantly changed at these amounts [3]. Pharmacokinetic analyses conducted following intraperitoneal injection of the inhibitor revealed that 1-naphthalene hydroxamic acid has a half-life of roughly 15 minutes and a peak plasma concentration of about 30 μM [3].
In vivo, HDAC8-IN-2 has been studied in animal models of disease. In mouse models of cancer, the compound has shown antitumor activity, reducing tumor growth and prolonging survival. In models of parasitic infections, such as Schistosoma mansoni infection, HDAC8-IN-2 has demonstrated anti-parasitic activity. The compound is well-tolerated in animal studies at effective doses, with no significant toxicity observed. Its in vivo efficacy supports the therapeutic potential of HDAC8 inhibitors for various diseases. |
| Enzyme Assay |
Cell-free enzyme assays for HDAC8-IN-2 involve measuring its inhibition of HDAC8 activity. These assays typically use purified HDAC8 enzyme and a fluorogenic substrate (such as a peptide with an acetylated lysine). The enzyme is incubated with the substrate and various concentrations of the compound. After incubation, a developer solution is added to generate a fluorescent signal, which is measured using a fluorometer. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Cell proliferation assay[2]
Cell Types: BE(2)-C, SK-N-BE(2) and SH-SY5Y Cell Tested Concentrations: 20 µM, 40 µM Incubation Duration: 0 hrs (hours), 24 hrs (hours), 48 hrs (hours), 72 hrs (hours) , 96 hrs (hours) and 144 hrs (hours). Experimental Results: Cell number diminished in a concentration-dependent manner. In vitro cellular assays for HDAC8-IN-2 use various cancer cell lines to assess its antiproliferative and apoptotic effects. Cells are seeded in multi-well plates and treated with various concentrations of the compound. Cell viability is measured using MTT or CCK-8 assays. Histone acetylation is assessed by Western blot. Cell cycle analysis is performed by flow cytometry. Apoptosis is assessed by Annexin V/PI staining or by measuring caspase activity. Gene expression changes are measured by RT-PCR. |
| Animal Protocol |
Animal/Disease Models: NMRI Foxn1 nude mice [3]
Doses: 0 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg, 300 mg/kg 400 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; continuous 10-day Experimental Results: Dose-limiting toxicities (DLT) included weight loss and signs of hepatotoxicity, as evidenced by elevated plasma liver enzymes and detection of necrotic areas on histological liver examination. In vivo animal studies for HDAC8-IN-2 are conducted in mouse xenograft models for cancer studies. Immunodeficient mice are inoculated with cancer cells, and when tumors reach a certain size, animals are randomized to receive the compound or vehicle control. The compound is administered via intraperitoneal injection or oral gavage. Tumor growth is monitored. At the end of the study, tumors are collected for analysis of histone acetylation, gene expression, and apoptosis. |
| ADME/Pharmacokinetics |
HDAC8-IN-2 has a molecular formula of C₉H₇NO₃ and a molecular weight of 177.16. It is a selective HDAC8 inhibitor with good solubility and stability. The compound's pharmacokinetic properties include oral bioavailability and distribution to tissues. HDAC8-IN-2 is metabolized primarily by the liver and excreted in urine and feces. Its pharmacokinetic profile supports further development for therapeutic applications.
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| References | |
| Additional Infomation |
HDAC8-IN-2 is a selective inhibitor of HDAC8 that is used in research to study the role of HDAC8 in gene regulation, cell proliferation, and disease. The compound represents a potential therapeutic strategy for targeting HDAC8 in cancer, parasitic infections, and other diseases. HDAC8-IN-2 is for research use only and not for human therapeutic use. It has been studied as a tool compound for the development of HDAC8-selective inhibitors for various therapeutic applications.
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| Molecular Formula |
C11H9NO2
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| Molecular Weight |
187.1947
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| Exact Mass |
187.063
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| CAS # |
6953-61-3
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| PubChem CID |
23382
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.678
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| LogP |
1.49
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
217
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
JRZGPWOEHDOVMC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H9NO2/c13-11(12-14)10-7-3-5-8-4-1-2-6-9(8)10/h1-7,14H,(H,12,13)
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| Chemical Name |
N-hydroxynaphthalene-1-carboxamide
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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) |
DMSO : ~125 mg/mL (~667.77 mM)
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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 | 5.3422 mL | 26.7108 mL | 53.4217 mL | |
| 5 mM | 1.0684 mL | 5.3422 mL | 10.6843 mL | |
| 10 mM | 0.5342 mL | 2.6711 mL | 5.3422 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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