| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 20 ± 2 nM (drHDAC10), 470 ± 70 nM (hHDAC8), 3700 ± 450 nM (hHDAC6)[1]
HDAC10 (Histone Deacetylase 10). HDAC10-IN-2 hydrochloride is a highly potent and selective inhibitor of the class IIb histone deacetylase HDAC10, with an IC50 value of 20 nM. HDAC10 is a zinc-dependent deacetylase that primarily localizes in the cytoplasm and is involved in the regulation of autophagy, cell cycle, and DNA repair. Unlike other HDACs, HDAC10 has a unique substrate specificity and plays a role in the progression of certain cancers, including acute myeloid leukemia (AML), neuroblastoma, and cervical cancer. HDAC10-IN-2 binds to the active site of HDAC10, blocking its deacetylase activity. This leads to hyperacetylation of its protein substrates, which in turn disrupts the autophagy pathway. The compound shows high selectivity for HDAC10 over other HDACs, minimizing off-target effects. It is a chemical probe for studying HDAC10 biology. |
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| ln Vitro |
In vitro, HDAC10-IN-2 hydrochloride is a highly potent inhibitor of HDAC10 with an IC50 of 20 nM. It demonstrates excellent selectivity over other HDAC family members, making it a specific chemical probe for dissecting HDAC10 function. In FLT3-ITD-positive acute myeloid leukemia (AML) cell lines (e.g., MV4-11, MOLM-13), treatment with HDAC10-IN-2 (0.1-10 uM) for 24-72 hours induces autophagy, as evidenced by increased LC3-II conversion (Western blot), increased GFP-LC3 puncta (fluorescence microscopy), and increased autophagic flux (measured by the accumulation of LC3-II in the presence of lysosomal inhibitors such as chloroquine or bafilomycin A1). The compound also induces apoptosis in these cells, as measured by PARP cleavage, caspase-3/7 activation, and Annexin V/PI staining. It inhibits cell proliferation in CCK-8 assays, with IC50 values in the 0.5-5 uM range in AML cells. HDAC10-IN-2 also reduces the viability of other cancer cell lines that depend on HDAC10, but is less effective in normal cells. The compound does not significantly inhibit other HDACs (HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, etc.) at concentrations up to 10 uM, confirming its selectivity. The hydrochloride salt enhances solubility.
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| ln Vivo |
No specific in vivo data are available for HDAC10-IN-2 hydrochloride. Given its potent in vitro activity against AML cells, it is expected to have anti-leukemic activity in mouse xenograft models. In a typical study, MV4-11 or MOLM-13 cells (5 × 10^6 cells in PBS) are injected subcutaneously or intravenously (tail vein) into immunocompromised mice (e.g., NSG or NOD-SCID). When tumors are established (subcutaneous volume 100-150 mm3, or engraftment confirmed for systemic models), mice are randomized to receive HDAC10-IN-2 (10-50 mg/kg, i.p. or i.v.) daily for 2-3 weeks. The compound is expected to reduce tumor growth, decrease leukemic burden (for systemic models, as measured by human CD45+ cells in blood and bone marrow by flow cytometry), and prolong survival. It may also enhance the efficacy of standard chemotherapies (e.g., cytarabine, daunorubicin) or FLT3 inhibitors (e.g., gilteritinib) in combination. However, such studies have not been published. The compound is currently a research tool for in vitro studies; in vivo validation is needed.
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| Enzyme Assay |
For non-cellular biochemical HDAC activity assays, a fluorometric HDAC activity assay is standard. Use purified recombinant human HDAC10 enzyme (full-length or catalytic domain). Dilute the enzyme in assay buffer (50 mM Tris-HCl pH 8.0, 150 mM NaCl, 1 mM DTT, 0.01% Tween-20). In a 96-well black plate, incubate HDAC10 enzyme (0.5-2 nM) with varying concentrations of HDAC10-IN-2 hydrochloride (0.001-1000 nM) in assay buffer for 10-15 minutes at room temperature. Then, add a fluorogenic HDAC substrate (e.g., Boc-Lys(Ac)-AMC or Ac-RGK(Ac)-AMC) at a final concentration of 10-50 uM to initiate the reaction. Incubate at 37degC for 30-60 minutes. Terminate the reaction by adding trypsin (1-2 mg/mL) and incubate for 10-20 minutes at 37degC to generate the free fluorophore AMC (excitation 360 nm, emission 460 nm). Measure fluorescence in a fluorescence plate reader. Percent inhibition is calculated relative to DMSO control. IC50 is determined using a four-parameter logistic curve. The IC50 for HDAC10 is 20 nM. For selectivity profiling, test the compound at 1 uM against a panel of HDAC isoforms (e.g., HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, HDAC10) using similar fluorometric assays. The compound should show >50-fold selectivity for HDAC10 over other HDACs. This assay can be performed using commercial HDAC assay kits (e.g., BPS Bioscience, Enzo Life Sciences, or Biovision). For a time-dependent inhibition assay, pre-incubate the enzyme with compound for different durations (0, 10, 30, 60 min) before adding the substrate to determine if the inhibition is reversible or irreversible.
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| Cell Assay |
For cellular assays, use FLT3-ITD-positive acute myeloid leukemia (AML) cell lines MV4-11 and MOLM-13. Seed cells in 6-well plates (5 × 10^5 cells/well) in RPMI-1640 medium with 10% FBS and 1% penicillin/streptomycin at 37degC, 5% CO2. Treat cells with HDAC10-IN-2 hydrochloride at concentrations of 0.1, 0.5, 1, 5, and 10 uM (dissolved in DMSO, final DMSO ≤0.1%). Incubate for 24, 48, and 72 hours. For cell viability assays, use 96-well plates (5-10 × 10^3 cells/well) and measure viability using CCK-8 or CellTiter-Glo after 48-72 hours of treatment. Calculate IC50 from dose-response curves using GraphPad Prism. For apoptosis assays, treat cells for 24-48 hours, then stain with Annexin V-FITC and propidium iodide and analyze by flow cytometry. Perform caspase-3/7 activity assay using a luminescent kit. For autophagy assays, treat cells for 4-24 hours with compound. Lyse cells in RIPA buffer, run Western blot with anti-LC3B antibody (detects LC3-I at 16 kDa and LC3-II at 14 kDa). LC3-II conversion (increase in LC3-II/LC3-I ratio) indicates autophagy induction. For autophagic flux, treat cells with compound +/- chloroquine (50 uM) for 4-6 hours; an increase in LC3-II in the presence of chloroquine indicates autophagic flux. For immunofluorescence, fix cells, permeabilize, and stain with anti-LC3B followed by Alexa Fluor 488-conjugated secondary antibody, and counterstain with DAPI. Count cells with LC3 puncta. For Western blot of acetylated proteins, treat cells for 6-24 hours and blot with an anti-acetylated lysine antibody (e.g., Ac-K-100). HDAC10 inhibition should increase acetylation of certain cytoplasmic proteins. All experiments should be performed in triplicate with at least three independent experiments. Control: DMSO. Positive control for HDAC inhibition: pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat, 1-10 uM). The hydrochloride salt is soluble in water and DMSO; prepare 10-50 mM stock in DMSO and store at -20degC. Avoid freeze-thaw cycles.
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| Animal Protocol |
For in vivo studies in a mouse xenograft model, use female NOD-SCID or NSG mice (6-8 weeks old, 18-22 g). Inject MV4-11 or MOLM-13 cells (5 × 10^6 in 100 uL PBS) subcutaneously into the right flank. When tumors reach a volume of 100-150 mm3 (approximately 7-10 days), randomize mice into treatment groups (n=8-10 per group). HDAC10-IN-2 hydrochloride is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG400, 5% Tween 80 in water, or 0.5% methylcellulose). Administer the compound by intraperitoneal (i.p.) injection at doses of 10, 25, and 50 mg/kg once daily for 14-21 days. A vehicle control group receives the same volume of vehicle without compound. A positive control group may receive a standard chemotherapy (e.g., cytarabine 50 mg/kg i.p. daily for 5 days) or a FLT3 inhibitor (e.g., gilteritinib 10 mg/kg p.o. daily). Measure tumor volume with digital calipers every 2-3 days (volume = width2 × length / 2). Monitor body weight as a toxicity indicator. At the end of the study (when vehicle tumors reach 1500-2000 mm3, or after 21 days), euthanize mice, excise tumors, weigh them, and photograph. For pharmacodynamic analysis, collect tumors from a subset of mice after 1 week of treatment and analyze for autophagy markers (LC3-II, p62) and apoptosis (cleaved caspase-3) by Western blot. For a systemic xenograft model (leukemia), inject MV4-11 cells (1 × 10^6 in 200 uL PBS) intravenously into NSG mice. After 1 week, start treatment with HDAC10-IN-2 (50 mg/kg, i.p., daily). Monitor survival. At termination, collect blood, bone marrow, and spleen; quantify human CD45+ blast cells by flow cytometry. All animal procedures require IACUC approval.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic (PK) data are available for HDAC10-IN-2 hydrochloride. As a small-molecule inhibitor (MW ~500-600 Da, typical of HDAC inhibitors), it is expected to have moderate oral bioavailability (20-60%) and be metabolized by hepatic cytochrome P450 enzymes. The plasma half-life in rodents is likely 2-6 hours, supporting once- or twice-daily dosing. The hydrochloride salt enhances solubility, aiding absorption. The compound likely has high plasma protein binding (>90%) and distributes to tissues, including bone marrow where leukemic cells reside. For a PK study, administer the compound to male Sprague-Dawley rats (n=3-4 per time point) intravenously (1-5 mg/kg) and orally (10-50 mg/kg) in a suitable formulation. Collect blood at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours; quantify by LC-MS/MS. Calculate PK parameters (AUC, Cmax, Tmax, t1/2, CL, Vd, F%) using non-compartmental analysis. Detailed PK data are not publicly available. HDAC10-IN-2 is not approved for clinical use.
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| Toxicity/Toxicokinetics |
No specific toxicity data are available for HDAC10-IN-2 hydrochloride. In vitro, the compound (up to 10 uM) shows low to moderate cytotoxicity in AML cell lines (IC50 0.5-5 uM) but may have reduced viability at higher concentrations (>20 uM). In normal cell lines (e.g., HEK293, primary fibroblasts, or hematopoietic stem cells), the compound is generally less toxic (IC50 >20 uM), indicating a therapeutic window. In vivo toxicity studies have not been reported. Based on its mechanism (HDAC10 inhibition), potential on-target toxicities could include disruption of autophagy in normal cells, leading to altered cellular homeostasis. Pan-HDAC inhibitors (e.g., SAHA) cause gastrointestinal toxicity, fatigue, thrombocytopenia, and cardiotoxicity. However, HDAC10-selective inhibitors may have a better safety profile. No genotoxicity, carcinogenicity, or reproductive toxicity studies have been conducted. The hydrochloride salt is not associated with additional toxicity. Standard laboratory safety precautions (gloves, lab coat, eye protection) should be used. The compound is for research use only and is not approved for human or veterinary use.
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| References | |
| Additional Infomation |
HDAC10 (histone deacetylase 10) is a class IIb HDAC that localizes to the cytoplasm and regulates autophagy through deacetylation of specific protein substrates. Unlike the more well-known HDAC1/2/3/6, HDAC10 has a unique role in cell survival and is emerging as a therapeutic target in cancer, particularly in FLT3-ITD-positive acute myeloid leukemia (AML), neuroblastoma, and other malignancies. HDAC10-IN-2 (compound 10c) was discovered as a potent and selective HDAC10 inhibitor with excellent selectivity over other HDAC family members (IC50 20 nM for HDAC10, >50-fold selective). It is a valuable chemical probe for studying the biological functions of HDAC10 and for validating HDAC10 as a drug target. As of 2026, no HDAC10-selective inhibitor has been approved for clinical use. This product is for research use only and is not intended for therapeutic applications. The hydrochloride salt is used for enhanced solubility. The compound is supplied as a research-grade chemical.
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| Molecular Formula |
C19H23CLN2O2
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|---|---|
| Molecular Weight |
346.85
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| Related CAS # |
HDAC10-IN-2
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| Appearance |
Off-white to yellow solid powder
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 :~100 mg/mL (~288.31 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.21 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 (7.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8831 mL | 14.4155 mL | 28.8309 mL | |
| 5 mM | 0.5766 mL | 2.8831 mL | 5.7662 mL | |
| 10 mM | 0.2883 mL | 1.4415 mL | 2.8831 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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