CSN5i-3 is a novel, highly selective and orally bioavailable inhibitor of CSN5/Jab1, inhibiting CSN-catalysed Cul1 deneddylation with an IC50 value of 5.8 nM.
Physicochemical Properties
| Molecular Formula | C28H29F2N5O2 |
| Molecular Weight | 505.5590 |
| Exact Mass | 505.228 |
| CAS # | 2375740-98-8 |
| Related CAS # | (R)-CSN5i-3;2863607-74-1 |
| PubChem CID | 129892190 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.35±0.1 g/cm3(Predicted) |
| Boiling Point | 666.5±55.0 °C(Predicted) |
| LogP | 4.3 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 37 |
| Complexity | 767 |
| Defined Atom Stereocenter Count | 2 |
| 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 |
| InChi Key | ANNKHJQLDMGQFM-UIOOFZCWSA-N |
| 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 |
| 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 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| 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]. |
| References |
[1]. Targeted inhibition of the COP9 signalosome for treatment of cancer. Nat Commun. 2016 Oct 24;7:13166. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 100 mg/mL (~197.80 mM) |
| 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 |