| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Tefinostat targets histone deacetylases (HDACs). It is a pan-HDAC inhibitor that promotes histone acetylation, leading to the reactivation of tumor suppressor genes, inhibition of cell proliferation, and induction of apoptosis in cancer cells. Tefinostat is a prodrug that is selectively activated in monocytes and macrophages by hCE-1, allowing for targeted intracellular accumulation.
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| ln Vitro |
Tefinostat (CHR-2845) (1-4 nM) has an EC50 value of 2.3 μM, 57 nM, 110 nM, and 560 nM, respectively, and is active against the AML cell lines HL60 (M2 FAB type), MV411 (M4, FLT3-ITD), OCIAML3 (M4 NPM1mut), and THP1 (M5) [1]. Tefinostat exhibits substantial growth inhibition and dose-dependent induction of apoptosis at 0, 0.5, 1, and 5μM for 24 and 48 hours [1].
In vitro, Tefinostat is a potent HDAC inhibitor. As a prodrug, it is cleaved into its active acid form, CHR-2847, by hCE-1. The active metabolite inhibits HDAC activity, leading to histone acetylation and changes in gene expression. The compound's targeted activation in monocytes and macrophages allows for cell-specific effects. Specific in vitro data, including IC50 values, are not extensively provided. |
| ln Vivo |
Tefinostat has been designed as an anti-cancer agent, particularly for hematological malignancies such as chronic myelomonocytic leukemia (CMML). Its targeted activation in monocytes and macrophages allows for selective accumulation in these cells. The compound promotes histone acetylation, leading to the reactivation of tumor suppressor genes, inhibition of cell proliferation, and induction of apoptosis in cancer cells.
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| Enzyme Assay |
In vitro enzyme assays for Tefinostat involve measuring HDAC activity. HDAC enzymes are incubated with histone substrates and acetyl-CoA in the presence of varying concentrations of Tefinostat or its active metabolite, CHR-2847. Histone acetylation is quantified by Western blot using anti-acetylated histone antibodies or by fluorometric assays. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
Cell viability assay [1]
Cell Types: AML cell line Tested Concentrations: 1-4 nM Incubation Duration: Experimental Results: Significant growth inhibition. Apoptosis analysis [1] Cell Types: Myeloid mononuclear cell line and HL60 Cell Tested Concentrations: 0, 0.5, 1 and 5μM Incubation Duration: 24, 48 hrs (hours) Experimental Results: In myeloid mononuclear cell line THP1, MV411 (FLT3-ITD) and OCIAML3 acted within 24 hrs (hours) and reached higher concentrations only in non-monocyte HL60 cells. For in vitro cell-based assays, monocyte/macrophage cell lines or primary cells are cultured and treated with Tefinostat at various concentrations. HDAC inhibition is assessed by measuring histone acetylation by Western blot. Cell proliferation is assessed using MTT or similar assays. Apoptosis is measured by Annexin V/PI staining or caspase activity assays. Gene expression changes are analyzed by qRT-PCR. |
| Animal Protocol |
In vivo animal studies for Tefinostat would typically use mouse models of hematological malignancies. The compound is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Tumor growth is monitored. Histone acetylation and gene expression changes are assessed in tumor tissues. The compound's targeted accumulation in monocytes and macrophages can be studied using tissue distribution analysis.
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| ADME/Pharmacokinetics |
Tefinostat has a molecular formula of benzeneacetic acid, α-(((4-((8-(hydroxyamino)-1,8-dioxooctyl)amino)phenyl)methyl)amino)-, cyclopentyl ester, (αS). It is a hydroxamic acid-derived HDAC inhibitor. Detailed pharmacokinetic parameters are not extensively characterized. The compound is for research use only.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Tefinostat are not extensively provided in the available literature. As an HDAC inhibitor, it would be expected to have a safety profile related to epigenetic modulation. The compound's targeted activation in monocytes and macrophages may reduce systemic toxicity. Standard toxicology assessments would be required for therapeutic development.
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| References | |
| Additional Infomation |
TefenoxaCortistatint is currently being investigated in the clinical trial NCT02759601 (Dose-escalation trial of tefenoxat for hepatocellular carcinoma (HCC)-associated inflammation). Tefenoxat is a hydroxamic acid-derived histone deacetylase (HDAC) inhibitor with potential antitumor activity. Tefenoxat inhibits HDAC, leading to the accumulation of highly acetylated histones, which may result in chromatin remodeling, inhibition of tumor oncogene transcription, suppression of tumor cell division, and induction of tumor cell apoptosis. HDAC is an enzyme upregulated in various tumor types that deacetylates chromatin histones; this drug may specifically target HDAC in monocyte-macrophage lineage cells.
Tefinostat (CHR-2845) is a monocyte/macrophage-targeted histone deacetylase (HDAC) inhibitor. It is a cell-permeant prodrug that is cleaved into its active acid form, CHR-2847, by the intracellular esterase human carboxylesterase-1 (hCE-1). It has been designed as an anti-cancer agent for hematological malignancies such as chronic myelomonocytic leukemia (CMML). No approved therapeutic status is reported. |
| Molecular Formula |
C28H37N3O5
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|---|---|
| Molecular Weight |
495.62
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| Exact Mass |
495.273
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| CAS # |
914382-60-8
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| PubChem CID |
15940949
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| Appearance |
White to off-white solid powder
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| LogP |
6.092
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
36
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| Complexity |
668
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CCC(C1)OC(=O)[C@H](C2=CC=CC=C2)NCC3=CC=C(C=C3)NC(=O)CCCCCCC(=O)NO
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| InChi Key |
GLNWREBYRLDPQP-MHZLTWQESA-N
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| InChi Code |
InChI=1S/C28H37N3O5/c32-25(14-6-1-2-7-15-26(33)31-35)30-23-18-16-21(17-19-23)20-29-27(22-10-4-3-5-11-22)28(34)36-24-12-8-9-13-24/h3-5,10-11,16-19,24,27,29,35H,1-2,6-9,12-15,20H2,(H,30,32)(H,31,33)/t27-/m0/s1
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| Chemical Name |
cyclopentyl (2S)-2-[[4-[[8-(hydroxyamino)-8-oxooctanoyl]amino]phenyl]methylamino]-2-phenylacetate
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| Synonyms |
CHR2845 CHR 2845 CHR-2845
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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 : ~100 mg/mL (~201.77 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.04 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 (5.04 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. View More
Solubility in Formulation 3: ≥ 0.83 mg/mL (1.67 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 | 2.0177 mL | 10.0884 mL | 20.1767 mL | |
| 5 mM | 0.4035 mL | 2.0177 mL | 4.0353 mL | |
| 10 mM | 0.2018 mL | 1.0088 mL | 2.0177 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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