CSN5i-3

Name: CSN5i-3
Brand: Tocris Bioscience
SKU: 7089

Tocris Bioscience, part of Bio-Techne | Catalog # 7089

COA / SDS

Potent and selective CSN5 (COP9 signalosome) inhibitor

Key Product Details

Description:	Potent and selective CSN5 (COP9 signalosome) inhibitor
Chemical Name:	3-(Difluoromethyl)-N-(6-((5S,6S)-6-hydroxy-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)-[1,10-biphenyl]-3-yl)-1-isopropyl-1H-pyrazole-5-carboxamide
Purity:	≥98% (HPLC)
Molecular Weight:	505.57

View Full Technical Details for CSN5i-3

Technical Data
Citations

Biological Activity for CSN5i-3

CSN5i-3 is a potent and selective CSN5 (COP9 signalosome) inhibitor. It inhibits deneddylation of NEDD8-modifed CRLs (IC₅₀ = 5.8 nM), keeping them in the neddylated state, and leading to inactivation of a subset of CRLs by inducing degradation of their substrate receptor module (SRM). In A2780 ovarian cancer cells, CSN5i-3 down-regulates the expression of COPS5 and arrest cells at S-phase. In HUVECs in vitro and in zebrafish embryos in vivo, CSN5i-3 induces endothelial barrier disruption and increases macromolecule leakage by increasing the expression and activity of RhoGTPases. CSN5i-3 also inhibits the growth of lymphoma cell xenografts in mice. Orally bioavailable.

The negative control CSN5i-3-NEG (Cat. No. 7532) is also available.

Scientific Data Examples for CSN5i-3

	Novartis vs Bio-Techne batch comparison for CSN5i-3 Effects of CSN5i-3 on a cancer cell line. (A) Concentration dependent effects (t = 3 days) of CSN5i-3. The IC₅₀ values are 26 nM and 16 nM for Novartis batch and Bio-Techne batch, respectively. (B) Cullins Cul4A level after treatment (t = 2 hours) with 100 nM of CSN5i-3 from either Novartis or Bio-Techne.

Technical Data for CSN5i-3

M. Wt	505.57
Formula	C₂₈H₂₉F₂N₅O₂
Storage	Store at -20°C
Purity	≥98% (HPLC)
CAS Number	2375740-98-8
PubChem ID	129892190
InChi Key	ANNKHJQLDMGQFM-UIOOFZCWSA-N
Smiles	CC(N1N=C(C(F)F)C=C1C(NC2=CC(C3=CC=CC=C3)=C([C@H]4[C@H](CCCC5=CN=CN45)O)C=C2)=O)C

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.

Tocris products are intended for laboratory research use only, unless stated otherwise.

Solubility for CSN5i-3

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
Solubility	DMSO	50.56	100

Preparing Stock Solutions for CSN5i-3

The following data is based on the product molecular weight 505.57.

Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.98 mL	9.89 mL	19.78 mL
5 mM	0.40 mL	1.98 mL	3.96 mL
10 mM	0.20 mL	0.99 mL	1.98 mL
50 mM	0.04 mL	0.20 mL	0.40 mL

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References for CSN5i-3

References are publications that support the biological activity of the product.

Zhange COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level. Biochem.Biophys.Res.Commun. 2017 PMID: 28919423
Majolée CSN5 inhibition triggers inflammatory signaling and Rho/ROCK-dependent loss of endothelial integrity. Sci.Rep. 2019 PMID: 31148579
Schlierf Targeted inhibition of the COP9 signalosome for treatment of cancer. Nat.Commun. 2016 PMID: 27774986