| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
HDAC1 4 nM (IC50) HDAC2 14 nM (IC50) HDAC3/SMRT 11 nM (IC50) HDAC6 15 nM (IC50) HDAC8 7 nM (IC50) HDAC10 20 nM (IC50)
CRA-026440 hydrochloride targets histone deacetylases (HDACs), a family of enzymes that remove acetyl groups from lysine residues on histones and other proteins. HDACs play critical roles in gene regulation, cell cycle control, and apoptosis. By inhibiting HDACs, CRA-026440 hydrochloride promotes the accumulation of acetylated histones and tubulin, leading to changes in gene expression and disruption of microtubule dynamics. The compound inhibits HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 with high potency. |
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| ln Vitro |
CRA-026440 hydrochloride has a GI50 value of 1.41 μM and inhibits the proliferation of HUVEC endothelial cells[1]. Apoptosis and tumor cell growth inhibition are induced by CRA-026440 hydrochloride (0.1-10 μM; 18 hours) through acetylated tubulin and histone buildup [1]. In vivo angiogenesis is inhibited in a dose-dependent manner by CRA-026440 hydrochloride (0.1-10 μM; 5 days) [1].
In vitro studies demonstrate that CRA-026440 hydrochloride is a potent broad-spectrum HDAC inhibitor. It inhibits HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 with Ki values of 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM, respectively. The compound has a GI50 value of 1.41 μM and inhibits the proliferation of HUVEC endothelial cells. CRA-026440 hydrochloride (0.1-10 μM; 18 hours) induces apoptosis and tumor cell growth inhibition through acetylated tubulin and histone buildup. |
| ln Vivo |
In mice with HCT116 or U937 human tumor xenografts, CRA-026440 hydrochloride (100 mg/kg; intravenously; daily; for three consecutive days) significantly reduced tumor growth [1].
No detailed in vivo activity data has been published for CRA-026440 hydrochloride. The compound has been primarily characterized in vitro as a potent broad-spectrum HDAC inhibitor with antitumor and anti-angiogenic activities. Its potent HDAC inhibitory activity (Ki values in the low nanomolar range) suggests that it could have potential for in vivo applications in cancer therapy. Further studies would be needed to evaluate its efficacy in animal models of cancer. |
| Enzyme Assay |
The HDAC inhibitory activity of CRA-026440 hydrochloride can be assessed using in vitro enzyme assays. In a typical assay, recombinant HDAC enzymes (HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, HDAC10) are incubated with a fluorogenic substrate and varying concentrations of CRA-026440 hydrochloride. The cleavage of the substrate releases a fluorescent product that is measured, and the Ki values are calculated. The Ki values for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM, respectively.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HCT116 cells Tested Concentrations: 0.1 μM, 0.5 μM, 1 μM, 5 μM, 10 μM Incubation Duration: 18 hrs (hours) Experimental Results: Resulted in the accumulation of both acetylated histones and acetylated tubulin. Induced expression of the cyclin-dependent kinase inhibitor p21Cip1/WAF1. The cellular activity of CRA-026440 hydrochloride is assessed using cancer cell lines and HUVEC endothelial cells. Cells are treated with varying concentrations of CRA-026440 hydrochloride (0.1-10 μM; 18 hours). Histone acetylation and tubulin acetylation are assessed by Western blotting using acetylated histone and acetylated tubulin antibodies. Apoptosis is assessed by annexin V/propidium iodide staining or caspase activation assays. Cell proliferation is measured using MTT or CellTiter-Glo assays. HUVEC proliferation is assessed to measure anti-angiogenic activity. |
| Animal Protocol |
Animal/Disease Models: HCT-116 tumor-bearing nude mice[1]
Doses: 100 mg/kg Route of Administration: iv; daily; for three days Experimental Results: Resulted in a statistically significant reduction in tumor growth. No detailed in vivo animal model data has been published for CRA-026440 hydrochloride. The compound has been primarily characterized in vitro as a potent broad-spectrum HDAC inhibitor. Future studies may involve the use of mouse xenograft models of cancer to assess the in vivo efficacy of CRA-026440 hydrochloride. The compound's anti-angiogenic activity suggests that it may be effective in combination with other anticancer agents. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data has been published for CRA-026440 hydrochloride. The compound has a molecular weight of 456.92 and a molecular formula of C23H25ClN4O4. It has a purity of >98%. The compound is typically stored at -20°C for up to 3 years as a powder or for 6 months in solution. Further studies would be needed to characterize its absorption, distribution, metabolism, and excretion properties.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for CRA-026440 hydrochloride. As a broad-spectrum HDAC inhibitor, the compound may have on-target effects on histone acetylation and gene expression in normal tissues. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development. The compound is intended for research use only.
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| References | |
| Additional Infomation |
CRA-026440 hydrochloride (CAS# 847459-98-7) is a potent and broad-spectrum HDAC inhibitor with Ki values of 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10, respectively. The compound induces apoptosis and tumor cell growth inhibition through acetylated tubulin and histone buildup. It has a GI50 of 1.41 μM against HUVEC endothelial cells and has antitumor and anti-angiogenic activities. The molecular formula is C23H25ClN4O4 and molecular weight is 456.92.
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| Molecular Formula |
C23H25CLN4O4
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|---|---|
| Molecular Weight |
456.922004461288
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| Exact Mass |
456.156
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| CAS # |
847459-98-7
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| Related CAS # |
CRA-026440;847460-34-8
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| PubChem CID |
11619469
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
32
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| Complexity |
678
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)CCOC1=CC2=C(C=C1)NC(=C2)C(=O)NCC#CC3=CC=C(C=C3)C(=O)NO.Cl
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| InChi Key |
RAAUQWIBVCZNFH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H24N4O4.ClH/c1-27(2)12-13-31-19-9-10-20-18(14-19)15-21(25-20)23(29)24-11-3-4-16-5-7-17(8-6-16)22(28)26-30;/h5-10,14-15,25,30H,11-13H2,1-2H3,(H,24,29)(H,26,28);1H
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| Chemical Name |
5-[2-(dimethylamino)ethoxy]-N-[3-[4-(hydroxycarbamoyl)phenyl]prop-2-ynyl]-1H-indole-2-carboxamide;hydrochloride
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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 (218.86 mM)
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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 | 2.1886 mL | 10.9428 mL | 21.8857 mL | |
| 5 mM | 0.4377 mL | 2.1886 mL | 4.3771 mL | |
| 10 mM | 0.2189 mL | 1.0943 mL | 2.1886 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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