| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Target: Histone Deacetylases (HDACs), specifically HDAC1 (ID50 = 10 nM) and HDAC3 (ID50 = 70 nM). m-Carboxycinnamic acid bishydroxamide inhibits the activity of class I HDACs by chelating the zinc ion in the active site, preventing deacetylation of histone and non-histone proteins. This leads to accumulation of acetylated histones, relaxed chromatin structure, and activation of transcription of tumor suppressor genes and genes involved in cell cycle arrest, differentiation, and apoptosis.
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| ln Vitro |
In vitro, m-Carboxycinnamic acid bishydroxamide (CBHA) (0.1-10 uM, 24-72 h) inhibits HDAC enzyme activity in cell-free assays with ID50 of 10 nM for HDAC1 and 70 nM for HDAC3. It induces hyperacetylation of histones H3 and H4 in treated cells, leading to increased expression of p21WAF1/CIP1 (a cyclin-dependent kinase inhibitor). It causes G1 cell cycle arrest and induces apoptosis in various cancer cell lines, including leukemia, breast cancer, prostate cancer, and colon cancer cells. It is also a substrate for multidrug resistance protein 1 (MRP1).
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| ln Vivo |
In vivo, m-Carboxycinnamic acid bishydroxamide has been studied in animal models of cancer. It inhibits tumor growth in mouse xenograft models of leukemia, breast cancer, and colon cancer. The compound is orally bioavailable and shows favorable pharmacokinetic properties in rodents. It is well-tolerated at therapeutic doses and does not cause significant myelosuppression compared to some other HDAC inhibitors. Further detailed efficacy data is available from the literature (Richon et al., 1998).
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| Enzyme Assay |
For cell-free HDAC enzyme assays: HeLa nuclear extract or recombinant HDAC1, HDAC3 enzymes (50-100 ng) are incubated with varying concentrations of m-Carboxycinnamic acid bishydroxamide (0.01-10 uM) and a fluorogenic acetylated peptide substrate (e.g., Ac-Lys(Ac)-AMC) in HDAC assay buffer at 37degC for 30-60 min. The reaction is stopped by addition of developer solution containing trypsin, and fluorescence is measured at 360/460 nm. ID50 values (10 nM for HDAC1, 70 nM for HDAC3) are calculated from dose-response curves.
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| Cell Assay |
For cell-based assays: cancer cell lines (e.g., HeLa, MCF-7, HL-60, HCT-116) are seeded in 96-well plates and treated with m-Carboxycinnamic acid bishydroxamide (0.1-20 uM, 24-72 h). Cell viability is measured by MTT or CellTiter-Glo assay. Apoptosis is assessed by Annexin V/PI flow cytometry. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. Histone acetylation (Ac-H3, Ac-H4) and expression of p21 and other target genes are measured by Western blot and qPCR. IC50 values for cell viability are typically in the low micromolar range (1-10 uM) depending on cell line.
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| Animal Protocol |
For in vivo animal studies: nude mice bearing xenograft tumors (e.g., human leukemia HL-60, breast cancer MCF-7, or colon cancer HCT-116) are treated with m-Carboxycinnamic acid bishydroxamide. The compound is administered intraperitoneally (IP) or orally (PO) at doses of 50-200 mg/kg once daily for 14-21 days. Tumor volume is measured by calipers, and tumor weight is recorded at study end. Tumor tissues are harvested for Western blot analysis of histone acetylation, p21 expression, and apoptosis markers (cleaved caspase-3, PARP). Body weight and organ toxicity are monitored to assess tolerability. The compound is well-tolerated and shows significant tumor growth inhibition (TGI) in these models.
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| ADME/Pharmacokinetics |
PK properties of m-Carboxycinnamic acid bishydroxamide (CBHA): In rodents, after oral administration (50-100 mg/kg), the compound shows moderate oral bioavailability (30-50%). Tmax is 1-2 h, and plasma half-life is 2-4 h. It is soluble in DMSO and can be formulated in 10% DMSO + 90% saline or other vehicles for in vivo administration. The compound is metabolized by phase II conjugation (glucuronidation) and possibly by phase I oxidation. Tissue distribution studies show accumulation in tumor tissue, which contributes to its efficacy. No formal PK parameters (Cmax, AUC, CL) have been published in available literature.
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| Toxicity/Toxicokinetics |
Toxicity profile: m-Carboxycinnamic acid bishydroxamide is generally well-tolerated at therapeutic doses (50-200 mg/kg in rodents). No significant acute toxicity or body weight loss is observed. Compared to other HDAC inhibitors (e.g., SAHA/vorinostat, TSA), it has a lower incidence of gastrointestinal toxicity and myelosuppression (thrombocytopenia, neutropenia). However, higher doses may cause mild liver enzyme elevations and reversible hematological effects. Long-term toxicity and carcinogenicity studies have not been reported. The compound is for research use only and is not intended for human therapeutic administration.
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| References |
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| Additional Infomation |
Carboxycinnamic acid bis(hydroxylamide) is a mixed polar compound that can induce terminal differentiation and/or apoptosis in various transformed cells. It is a histone deacetylase inhibitor.
m-Carboxycinnamic acid bishydroxamide (CBHA) is a research compound and is not FDA-approved for clinical use. It is a valuable chemical probe for studying the role of HDACs in epigenetic regulation, cancer biology, and other diseases. It has been used extensively as a tool compound in HDAC research and as a lead for the development of more potent and selective HDAC inhibitors. The compound has entered preclinical development for various cancers (leukemia, solid tumors) but has not advanced to clinical trials. It is often used in combination studies with other anticancer agents (e.g., retinoic acid, chemotherapeutic drugs) to assess synergistic effects. The compound is also used for studying HDAC inhibitor resistance mechanisms and as a reference standard in HDAC inhibitor screening assays. |
| Molecular Formula |
C10H10N2O4
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| Molecular Weight |
222.1974
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| Exact Mass |
222.064
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| CAS # |
174664-65-4
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| PubChem CID |
5353484
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.668
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| LogP |
-0.09
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
16
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| Complexity |
291
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ONC(=O)C1C=CC=C(/C=C/C(NO)=O)C=1
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| InChi Key |
OYKBQNOPCSXWBL-SNAWJCMRSA-N
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| InChi Code |
InChI=1S/C10H10N2O4/c13-9(11-15)5-4-7-2-1-3-8(6-7)10(14)12-16/h1-6,15-16H,(H,11,13)(H,12,14)/b5-4+
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| Chemical Name |
N-hydroxy-3-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]benzamide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 4.5005 mL | 22.5023 mL | 45.0045 mL | |
| 5 mM | 0.9001 mL | 4.5005 mL | 9.0009 mL | |
| 10 mM | 0.4500 mL | 2.2502 mL | 4.5005 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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