| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
CSN5i-3 targets CSN5/Jab1, the catalytic subunit of the COP9 signalosome (CSN) complex. The CSN complex regulates the activity of cullin-RING ubiquitin ligases (CRLs) by removing the ubiquitin-like modifier NEDD8 from cullin subunits (deneddylation). By inhibiting CSN5, CSN5i-3 blocks CSN-catalyzed Cul1 deneddylation, leading to accumulation of neddylated cullins and disruption of CRL activity. This affects the ubiquitination and degradation of various substrates involved in cell cycle regulation and other processes.
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| ln Vitro |
By causing the breakdown of their substrate recognition modules, CSN5i-3 traps CRLs in the neddylated state, which deactivates a portion of CRLs [1].
In vitro, CSN5i-3 has been shown to inhibit CSN-catalyzed Cul1 deneddylation with an IC50 of 5.8 nM. The compound is selective for CSN5 and has been shown to have cytotoxic effects on various cancer cell lines. CSN5i-3 is being studied as a potential anticancer agent due to its ability to disrupt CRL activity and affect cell proliferation and survival. |
| ln Vivo |
CSN5i-3 demonstrated good pharmacokinetic characteristics. CSN5i-3 administration causes the production of cleaved PARP and cleaved caspase 3, indicating induction of apoptosis [1].
In vivo, CSN5i-3 is orally bioavailable and has been studied in preclinical models of cancer. The compound has shown potential as an anticancer agent by inhibiting CSN5 activity and disrupting CRL-mediated protein degradation. Further in vivo studies are ongoing to evaluate its efficacy and safety in various cancer models. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for CSN5i-3 measures its ability to inhibit CSN-catalyzed Cul1 deneddylation. The assay is performed using purified CSN complex and neddylated Cul1 as substrate, and the reaction is monitored by Western blot for neddylated Cul1 or by other suitable methods. IC50 values are calculated from dose-response curves. Selectivity is assessed by testing the compound against other proteases or related targets.
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| Cell Assay |
In vitro cellular studies are conducted using various cancer cell lines. Cells are treated with CSN5i-3 at various concentrations (typically nM to μM ranges) for defined time periods. Cell viability is assessed using MTT or CellTiter-Glo assays. CSN activity and Cul1 neddylation status are measured by Western blot. Cell cycle analysis and apoptosis assays are performed to evaluate mechanisms of cell death.
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| Animal Protocol |
In vivo animal experiments are performed using xenograft models of cancer. Tumor-bearing mice are administered CSN5i-3 via oral gavage at various doses. Tumor volume is measured over time, and endpoints include tumor growth inhibition and survival. Pharmacodynamic studies evaluate CSN5 inhibition and Cul1 neddylation status in tumor tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of CSN5i-3 include oral bioavailability and solubility in DMSO (≥90 mg/mL). The compound has a molecular weight of 505.56 g/mol and molecular formula C28H29F2N5O2. Storage at -20°C, protected from light and sealed, is recommended. The compound should be protected from moisture and light. For in vivo administration, appropriate formulations should be used.
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| Toxicity/Toxicokinetics |
Toxicological data for CSN5i-3 are derived from preclinical studies. The compound is for research use only and not intended for human therapeutic applications. No significant toxicity has been reported at effective doses in animal studies. Standard safety precautions should be followed when handling the compound due to its potent biological activity. Long-term toxicity and carcinogenicity studies have not been conducted.
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| References | |
| Additional Infomation |
CSN5i-3 is a potent, selective, and orally bioavailable inhibitor of CSN5/Jab1 with an IC50 of 5.8 nM for CSN-catalyzed Cul1 deneddylation. The compound has the molecular formula C28H29F2N5O2 and molecular weight of 505.56 g/mol. It has been shown to have cytotoxic effects on various cancer cells and is being studied as a potential anticancer agent. The compound is supplied as a powder with >99% purity and should be stored under recommended conditions. It is not for human use and is intended for research purposes only.
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| Molecular Formula |
C28H29F2N5O2
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|---|---|
| Molecular Weight |
505.5590
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| Exact Mass |
505.228
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| CAS # |
2375740-98-8
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| Related CAS # |
(R)-CSN5i-3;2863607-74-1
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| PubChem CID |
129892190
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.35±0.1 g/cm3(Predicted)
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| Boiling Point |
666.5±55.0 °C(Predicted)
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
767
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)N1C(=CC(=N1)C(F)F)C(=O)NC2=CC(=C(C=C2)[C@H]3[C@H](CCCC4=CN=CN34)O)C5=CC=CC=C5
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| InChi Key |
ANNKHJQLDMGQFM-UIOOFZCWSA-N
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| InChi Code |
InChI=1S/C28H29F2N5O2/c1-17(2)35-24(14-23(33-35)27(29)30)28(37)32-19-11-12-21(22(13-19)18-7-4-3-5-8-18)26-25(36)10-6-9-20-15-31-16-34(20)26/h3-5,7-8,11-17,25-27,36H,6,9-10H2,1-2H3,(H,32,37)/t25-,26-/m0/s1
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| Chemical Name |
5-(difluoromethyl)-N-[4-[(5S,6S)-6-hydroxy-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl]-3-phenylphenyl]-2-propan-2-ylpyrazole-3-carboxamide
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 (~197.80 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.95 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 (4.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9780 mL | 9.8900 mL | 19.7800 mL | |
| 5 mM | 0.3956 mL | 1.9780 mL | 3.9560 mL | |
| 10 mM | 0.1978 mL | 0.9890 mL | 1.9780 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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