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| Targets |
HDAC1 100 nM (ID50)
Histone deacetylase 1 (HDAC1). Pyroxamide is a potent inhibitor of HDAC1 with an IC50 of 100 nM. HDAC1 is a class I histone deacetylase that removes acetyl groups from histone lysine residues, leading to chromatin condensation and transcriptional repression. By inhibiting HDAC1, Pyroxamide promotes histone hyperacetylation, which opens chromatin structure and reactivates the expression of tumor suppressor genes and other genes involved in cell cycle regulation and apoptosis. The compound's hydroxamic acid moiety chelates the zinc ion in the HDAC active site, blocking the enzyme's deacetylase activity. This mechanism is shared by other hydroxamic acid-based HDAC inhibitors such as suberoylanilide hydroxamic acid (SAHA, vorinostat). Pyroxamide may also inhibit other HDAC isoforms, though its selectivity profile is not extensively characterized in the available literature. |
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| ln Vitro |
Pyroxamide (1.25 -20.0 μM; 24-72 hours) suppresses the development of RH30B and RD cells, resulting in 44% dead cells at 20.0 μM and 86% dead cells in culture after 72 hours [1]. Pyroxamide (10.0 – 20.0 μM; 48 hours) exhibits sub-G1 fractions of 45.0% and 72.3% at 10.0 and 20.0 μM, in that order [1].
Pyroxamide demonstrates potent in vitro activity against HDAC1 with an IC50 of 100 nM. In cell-based assays, the compound induces apoptosis and cell cycle arrest in leukemia cells. The compound's ability to inhibit HDAC activity can be assessed by measuring histone acetylation levels in treated cells via Western blot, with increased acetylation indicating HDAC inhibition. Pyroxamide's anti-proliferative effects have been demonstrated in various cancer cell lines, with the compound showing potential anti-cancer properties. The compound's hydroxamic acid moiety is essential for its HDAC inhibitory activity, as it chelates the catalytic zinc ion in the enzyme active site. Further detailed in vitro data, including IC50 values against other HDAC isoforms and selectivity profiles, are not extensively reported in the available literature. |
| ln Vivo |
In vivo activity of Pyroxamide has been suggested by its mechanism of action as an HDAC inhibitor. HDAC inhibitors have been shown to have anti-tumor activity in various preclinical models, and Pyroxamide's ability to induce apoptosis and cell cycle arrest in leukemia cells suggests potential in vivo efficacy. However, specific in vivo data for Pyroxamide, including efficacy in animal models, pharmacokinetics, and toxicity, are not extensively reported in the available literature. The compound is primarily a research tool for studying HDAC biology and evaluating the therapeutic potential of HDAC inhibition in cancer. Further studies would be needed to fully characterize its in vivo activity and therapeutic potential.
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| Enzyme Assay |
Enzyme inhibition assays for Pyroxamide are performed using recombinant HDAC1 enzyme. The compound is incubated with the enzyme and a fluorogenic substrate (typically a peptide containing an acetylated lysine residue), and the inhibition of deacetylase activity is measured by monitoring the increase in fluorescence upon substrate deacetylation. The IC50 value of 100 nM is determined from dose-response curves. Selectivity against other HDAC isoforms can be assessed using similar assays with recombinant HDAC2, HDAC3, HDAC6, and other isoforms. The compound's mechanism of action—zinc chelation by the hydroxamic acid moiety—can be confirmed by competition assays with zinc or by comparing activity against HDAC mutants with altered zinc coordination.
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: RD cells; RH30B cells Tested Concentrations: 1.25-20.0 μM Incubation Duration: 24 hrs (hours); 48 hrs (hours); 72 hrs (hours) Experimental Results: Resulted in a cell growth decrease in RD and RH30B cells. Cell Cycle Analysis[2] Cell Types: RD cells; RH30B cells Tested Concentrations: 10.0 μM; 20.0 μM Incubation Duration: 48 hrs (hours) Experimental Results: Increased the sub-G1 fractions at 48 hrs (hours) compared with control samples. Cell-based assays for Pyroxamide are conducted using various cancer cell lines, particularly leukemia cell lines. Cells are treated with Pyroxamide at various concentrations (typically ranging from nanomolar to micromolar) for defined time periods (24-72 hours), and the following endpoints are assessed: histone acetylation levels (by Western blot), cell viability (by MTT or CellTiter-Glo), apoptosis (by annexin V staining or caspase activation), and cell cycle distribution (by flow cytometry). The compound's anti-proliferative effects are evaluated by measuring IC50 values for cell growth inhibition. The specificity of the observed effects can be confirmed by comparing with other HDAC inhibitors or by using HDAC-overexpressing or knockdown cell lines. |
| Animal Protocol |
In vivo studies for Pyroxamide would typically involve administration to mouse models of cancer, such as leukemia xenografts. The compound would be administered via various routes (e.g., oral, intraperitoneal, intravenous) at defined doses and schedules. Pharmacodynamic endpoints would include measurement of histone acetylation in tumor tissues, assessment of tumor growth inhibition, and evaluation of survival. Pharmacokinetic parameters such as plasma concentration-time profiles, half-life, clearance, and bioavailability would be determined from serial blood sampling. However, specific in vivo data for Pyroxamide are not extensively reported in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Pyroxamide are not extensively reported in the available literature. As a small molecule HDAC inhibitor with a molecular weight of 265.31, the compound would be expected to have reasonable oral bioavailability if administered orally, though this would need to be confirmed experimentally. The compound's hydroxamic acid moiety may be susceptible to metabolic clearance, which is common among hydroxamic acid-based HDAC inhibitors. Storage recommendations include standard conditions for research compounds. Further PK characterization would be required for comprehensive profiling.
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| Toxicity/Toxicokinetics |
Toxicological data for Pyroxamide are not extensively reported in the available literature. The compound is intended for research use only and is not approved for clinical use. HDAC inhibitors as a class can have dose-limiting toxicities including fatigue, gastrointestinal effects, and myelosuppression, though the specific toxicity profile of Pyroxamide would need to be determined in preclinical toxicology studies. Standard laboratory safety precautions should be followed when handling the compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety glasses) and proper ventilation.
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| References |
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| Additional Infomation |
N'-Hydroxy-N-(3-pyridyl)octanediamide is an aromatic amide. Pyronamide has been used in clinical trials for the treatment of various diseases, including leukemia, lymphoma, small intestinal cancer, precancerous lesions, and myelodysplastic syndromes. Pyronamide is a synthetic derivative of hydroxamic acid and possesses antitumor properties. Pyronamide inhibits histone deacetylases involved in transcription; induces excessive acetylation of core histones, thereby regulating chromatin structure and affecting the transcription of certain genes that suppress tumor growth; and induces cell growth arrest and apoptosis. Pyronamide is being used in clinical trials for cancer chemotherapy. (NCI04)
Pyroxamide is a potent HDAC1 inhibitor (IC50 = 100 nM) with potential anti-cancer properties. It belongs to the hydroxamic acid class of HDAC inhibitors and induces apoptosis and cell cycle arrest in leukemia cells. The compound is a research tool for studying HDAC biology and evaluating the therapeutic potential of HDAC inhibition in cancer. It is not approved for clinical use and has no marketed drug products. Synonyms include N-hydroxy-N'-3-pyridinyloctanediamide and N1-hydroxy-N8-(pyridin-3-yl)octanediamide. The compound is available from multiple chemical suppliers. |
| Molecular Formula |
C13H19N3O3
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|---|---|
| Molecular Weight |
265.31
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| Exact Mass |
265.142
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| CAS # |
382180-17-8
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| PubChem CID |
4996
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.570
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| LogP |
0.04
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
19
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| Complexity |
284
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PTJGLFIIZFVFJV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H19N3O3/c17-12(15-11-6-5-9-14-10-11)7-3-1-2-4-8-13(18)16-19/h5-6,9-10,19H,1-4,7-8H2,(H,15,17)(H,16,18)
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| Chemical Name |
N'-hydroxy-N-pyridin-3-yloctanediamide
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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 (471.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.84 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 20.8 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: ≥ 2.08 mg/mL (7.84 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7692 mL | 18.8459 mL | 37.6918 mL | |
| 5 mM | 0.7538 mL | 3.7692 mL | 7.5384 mL | |
| 10 mM | 0.3769 mL | 1.8846 mL | 3.7692 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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