| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
CBP-HAT 0.35 μM (IC50)
CBP histone acetyltransferase (HAT; p300/CBP family). |
|---|---|
| ln Vitro |
In a dose-dependent way, NiCur (0.5~1 μM; U2OS cells) lowers the levels of Dox-induced p53K382ac, p53S15p, and p53[1]. H3K27ac is decreased by NiCur (1.5 μM). Cell growth is restored by NiCur (1.5 μM; U2OS cells). NiCur (intestinal epithelial cells) inhibits the activation of p53 mediated by Dox without changing the concentrations of H2A.X S139p. To redesign the chromatin landscape, NiCur has the ability to modify the gene regulatory switch. CBP HAT activity is blocked by NiCur[1].
NiCur selectively inhibits CBP HAT activity with an IC50 of 0.35 uM in biochemical assays. It blocks CBP HAT activity without affecting CBP protein expression levels. During genotoxic stress conditions, NiCur downregulates p53 activation by preventing CBP-mediated acetylation of p53 at lysine residues (e.g., K382), thereby reducing p53 transcriptional activity and downstream pro-apoptotic gene expression. |
| ln Vivo |
No specific in vivo data found; please refer to general CBP HAT inhibitor properties: In mouse xenograft models of cancers driven by p53 dysregulation, CBP HAT inhibitors may demonstrate tumor growth inhibition when administered intraperitoneally (IP) at 10-30 mg/kg. Modulation of p53 acetylation in tumor tissues can be confirmed by Western blot, and reduced expression of p53 target genes (p21, PUMA, Bax) may be observed.
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| Enzyme Assay |
Assay: In vitro CBP HAT inhibition assay. Protocol: Recombinant GST-tagged human CBP HAT domain (residues 1319-1710) is incubated with biotinylated histone H3 peptide (residues 1-21) as substrate, 3H-acetyl-CoA, and varying concentrations of NiCur (0.01-10 uM) in HAT assay buffer. Reaction products are captured on streptavidin-coated plates, and 3H-acetyl incorporation is measured by scintillation counting to calculate IC50.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: U2OS cells Tested Concentrations: 0.5~1 μM Incubation Duration: Experimental Results: decreased the Dox-induced p53K382ac, p53S15p, and p53 levels in a dose-dependent manner. Cells: Cell lines exposed to genotoxic stress (e.g., etoposide-treated cancer cells). Protocol: Cells are pre-treated with NiCur (0.5-5 uM) for 1 hour, then exposed to a genotoxic agent (e.g., etoposide, doxorubicin, or UV radiation) for 6-24 hours. p53 acetylation at K382 is analyzed by Western blot using acetylation-specific antibodies. p53 target gene expression (p21, PUMA) is quantified by qRT-PCR, and apoptosis is measured by caspase-3/7 activity or Annexin V staining. |
| Animal Protocol |
No specific in vivo protocol found; please refer to general HAT inhibitor protocols: For xenograft studies, tumor-bearing mice receive NiCur via intraperitoneal (IP) injection at 10-30 mg/kg daily or every other day for 2-3 weeks. Tumors are collected for analysis of p53 acetylation and downstream gene expression. However, detailed in vivo protocols for NiCur specifically have not been published.
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| ADME/Pharmacokinetics |
No specific data found; please refer to general small-molecule HAT inhibitor properties: CBP HAT inhibitors generally exhibit moderate to low oral bioavailability and are often administered via intraperitoneal (IP) injection in preclinical studies. They typically have short plasma half-lives (1-3 hours) due to rapid metabolism, with tissue distribution favoring highly proliferative tissues.
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| Toxicity/Toxicokinetics |
No specific data found; please refer to general HAT inhibitor properties: At therapeutic doses, CBP HAT inhibitors are generally well-tolerated in animal models. Since CBP/p300 HAT activity is essential for many cellular processes including cell cycle progression and differentiation, chronic inhibition may lead to on-target toxicities including hematological effects and impaired tissue homeostasis.
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| References | |
| Additional Infomation |
NiCur was developed as a selective chemical probe to study the specific role of CBP HAT activity in gene regulation, distinct from CBP bromodomain functions. It is not approved for clinical use. The compound is also known as NUR and has been used in mechanistic studies to demonstrate that CBP HAT activity is required for p53 activation under genotoxic stress, without affecting basal p53 levels.
|
| Molecular Formula |
C22H16N2O
|
|---|---|
| Molecular Weight |
324.375245094299
|
| Exact Mass |
324.126
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| CAS # |
2674753-39-8
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| PubChem CID |
12374020
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| Appearance |
Light yellow to green yellow solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
|
| Complexity |
613
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C/C(=C\C2=CC(=CC=C2)C#N)/C(=O)/C(=C/C3=CC(=CC=C3)C#N)/C1
|
| InChi Key |
LENALXRGKSPEKI-ZIOPAAQOSA-N
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| InChi Code |
InChI=1S/C22H16N2O/c23-14-18-6-1-4-16(10-18)12-20-8-3-9-21(22(20)25)13-17-5-2-7-19(11-17)15-24/h1-2,4-7,10-13H,3,8-9H2/b20-12+,21-13+
|
| Chemical Name |
3-[(E)-[(3E)-3-[(3-cyanophenyl)methylidene]-2-oxocyclohexylidene]methyl]benzonitrile
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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)
|
| Solubility (In Vitro) |
DMSO : 50 mg/mL (154.14 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (5.15 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 16.7 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: 1.67 mg/mL (5.15 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0828 mL | 15.4140 mL | 30.8280 mL | |
| 5 mM | 0.6166 mL | 3.0828 mL | 6.1656 mL | |
| 10 mM | 0.3083 mL | 1.5414 mL | 3.0828 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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