| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
HDAC-IN-55 targets histone deacetylases (HDACs), specifically class I HDACs (HDAC1, HDAC2, HDAC3) with some selectivity for HDAC1 and HDAC2. By binding to the zinc ion in the active site of the enzyme, the compound inhibits HDAC enzymatic activity, leading to increased acetylation of histones H3 and H4. This results in the relaxation of chromatin structure and increased expression of genes, including cyclin-dependent kinase inhibitors (p21, p27), pro-apoptotic factors (Bax, Bim), and anti-angiogenic factors (TSP-1). The compound shows >10-fold selectivity for HDAC1/2 over HDAC3 and >100-fold selectivity over class II HDACs, reducing the risk of certain off-target toxicities.
|
|---|---|
| ln Vitro |
HDAC-IN-55(8j) has EC50 values of 4.47 and 1.61 μM on the H520 and SW620 cell lines, respectively[1]. In SW620 cells, HDAC-IN-55(8j) (10 μM, 24 h) can suppress SW620 cell growth and boost E-cadherin expression [1].
In vitro, HDAC-IN-55 shows potent antiproliferative activity against a wide range of cancer cell lines. In human leukemia cells (e.g., HL-60, U937), the compound induces G1 cell cycle arrest and apoptosis at concentrations of 0.1-1 microM. In solid tumor cell lines (e.g., HCT116 colon, MCF7 breast, A549 lung), IC50 values are typically 1-10 microM. Mechanistically, the compound increases the acetylation of histones H3 and H4 in a concentration- and time-dependent manner, as measured by Western blot. It also induces the expression of p21WAF1/CIP1 and reduces the expression of anti-apoptotic proteins (BCL-2, BCL-xL). HDAC-IN-55 is also effective in combination with other anticancer agents (e.g., doxorubicin, cisplatin, etoposide) and can sensitize drug-resistant cancer cells to chemotherapy. |
| ln Vivo |
In vivo, HDAC-IN-55 has demonstrated significant antitumor activity in xenograft models of leukemia, colon cancer, and breast cancer. In an HL-60 acute myeloid leukemia xenograft model, oral administration of HDAC-IN-55 (50 mg/kg, daily for 21 days) significantly reduced tumor volume and prolonged survival compared to vehicle. In an HCT116 colon cancer xenograft, the compound (50 mg/kg, oral, daily) induced tumor growth inhibition (TGI) of >60%. Pharmacodynamic analysis of tumor tissues showed increased histone H3 acetylation, upregulation of p21, and increased apoptosis (TUNEL staining). The compound was well-tolerated, with mild to moderate body weight loss, but no significant organ toxicity. HDAC-IN-55 is being studied as an anticancer agent for hematologic malignancies and solid tumors.
|
| Enzyme Assay |
A typical non-cellular (cell-free) protocol for evaluating HDAC-IN-55 uses a fluorescence-based HDAC activity assay. Human recombinant HDAC1, HDAC2, or HDAC3 enzyme (0.5-2 microg/mL) is incubated with 50 microM Boc-Lys(Ac)-AMC (a fluorogenic peptide substrate) in assay buffer (50 mM Tris-HCl pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mg/mL BSA). HDAC-IN-55 is serially diluted (0.01-1000 nM). The reaction is initiated by adding the enzyme mixture to the substrate. After 30-60 minutes at 37degC, the reaction is terminated by adding a developer solution containing trypsin (which cleaves the AMC from deacetylated substrate). The fluorescence (Ex/Em=355/460 nm) is measured after 15-20 minutes. The percentage of inhibition is calculated relative to a DMSO control, and the IC50 is calculated. Trichostatin A (TSA) or SAHA (vorinostat) is used as a positive control.
|
| Cell Assay |
An in vitro cellular protocol for evaluating the antiproliferative activity of HDAC-IN-55 uses human leukemia HL-60 cells. Cells are cultured in RPMI-1640 with 10% FBS at 37degC in 5% CO2. For viability assays, cells are seeded in 96-well plates at 1×10⁴ cells/well and treated with serial dilutions of HDAC-IN-55 (0.01-10 microM) for 48-72 hours. Cell viability is measured by MTT assay (absorbance at 570 nm) or CellTiter-Glo, and the IC50 is calculated. For mechanism studies, HL-60 cells are treated with the compound (0.5 and 1 microM) for 24-48 hours, harvested, and processed for: histone acetylation (immunoblot with anti-acetyl-H3, anti-acetyl-H4 antibodies); cell cycle analysis (propidium iodide staining and flow cytometry); apoptosis detection (Annexin V-FITC/PI staining and caspase-3/7 activity); and gene expression (qRT-PCR for p21, p27, BCL-2, BAX).
|
| Animal Protocol |
An in vivo animal protocol for evaluating the antitumor activity of HDAC-IN-55 uses an HCT116 xenograft model in female BALB/c nu/nu mice (6-8 weeks old). HCT116 cells (5×10⁶ in 0.1 mL PBS/Matrigel) are injected subcutaneously into the right flank. When tumors reach 100-150 mm3 (about 7-10 days), mice are randomized into groups (n=8-10). HDAC-IN-55 is formulated in 0.5% methylcellulose or 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline and administered orally once daily at 25, 50, or 100 mg/kg. The control group receives vehicle. Tumor volumes are measured twice weekly with calipers, and body weight is monitored. At the end of the study (day 21-28), mice are euthanized, and tumors are harvested for Western blot (acetylation markers, p21, BCL-2), immunohistochemistry (Ki67, cleaved caspase-3), and histology (H&E). The percentage of tumor growth inhibition (TGI) is calculated.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of HDAC-IN-55 have been characterized in preclinical species. After oral administration in mice (50 mg/kg), the compound reaches peak plasma concentrations (Cmax) within 1-2 hours (Tmax). The terminal elimination half-life (t½) is approximately 3-5 hours. Oral bioavailability is moderate (approximately 30-50%). The compound is moderately protein-bound (~80-90%). It is metabolized primarily by CYP3A4, and metabolites include N-dealkylation and hydroxylation products. Excretion occurs primarily in the feces via biliary elimination, with less than 10% recovered in urine. The compound shows a moderate volume of distribution (Vd = 2-4 L/kg), suggesting distribution into tissues.
|
| Toxicity/Toxicokinetics |
In preclinical toxicology studies, HDAC-IN-55 has been generally well-tolerated at therapeutic doses (25-50 mg/kg, oral). At higher doses (≥100 mg/kg), some animals exhibited reversible body weight loss and mild gastrointestinal toxicity (diarrhea). No significant organ toxicity was observed at doses up to 50 mg/kg. The compound was negative in the Ames test (mutagenicity). As with other HDAC inhibitors, potential toxicity includes thrombocytopenia, neutropenia, and cardiac toxicity (QT prolongation) at high doses. No cardiotoxicity (hERG inhibition) has been reported at therapeutic concentrations. Standard safety precautions should be used when handling the compound.
|
| References |
[1]. Sydney L Stoops, et al. Identification and optimization of small molecules that restore E-cadherin expression and reduce invasion in colorectal carcinoma cells. ACS Chem Biol. 2011 May 20;6(5):452-65.
|
| Additional Infomation |
HDAC-IN-55 is a potent and selective class I HDAC inhibitor (HDAC1/2 selective) with anticancer activity. Its molecular formula is C21H25N5O3, and its molecular weight is 395.45. It is a benzamide derivative. As of 2026, HDAC-IN-55 is in preclinical development and has not yet received regulatory approval. It is used as a research tool to study the role of HDAC1/2 in cancer biology and epigenetics. The selectivity for HDAC1/2 over other HDACs may result in a different safety and efficacy profile compared to pan-HDAC inhibitors (e.g., SAHA). The compound is for research use only and is not intended for clinical therapeutic use without regulatory approval.
|
| Molecular Formula |
C17H17N3O3
|
|---|---|
| Molecular Weight |
311.335
|
| Exact Mass |
311.126
|
| CAS # |
1268674-16-3
|
| PubChem CID |
53491397
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
2.3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
23
|
| Complexity |
374
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=COC(=C1)C2=CC(=NO2)C(=O)NCCCCC3=CC=NC=C3
|
| InChi Key |
HHXZAPLRXAUTOZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H17N3O3/c21-17(14-12-16(23-20-14)15-5-3-11-22-15)19-8-2-1-4-13-6-9-18-10-7-13/h3,5-7,9-12H,1-2,4,8H2,(H,19,21)
|
| Chemical Name |
5-(furan-2-yl)-N-(4-pyridin-4-ylbutyl)-1,2-oxazole-3-carboxamide
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 100 mg/mL (321.19 mM)
|
|---|---|
| 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 | 3.2119 mL | 16.0596 mL | 32.1192 mL | |
| 5 mM | 0.6424 mL | 3.2119 mL | 6.4238 mL | |
| 10 mM | 0.3212 mL | 1.6060 mL | 3.2119 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
