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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)
Literature (3)

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

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
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 Data for CSN5i-3

Solvent Max Conc. mg/mL Max Conc. mM
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.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.98 mL 9.89 mL 19.78 mL
5 mM 0.4 mL 1.98 mL 3.96 mL
10 mM 0.2 mL 0.99 mL 1.98 mL
50 mM 0.04 mL 0.2 mL 0.4 mL

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References for CSN5i-3

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

Schlierf et al (2016) Targeted inhibition of the COP9 signalosome for treatment of cancer. Nat.Commun. 7 13166 PMID: 27774986

Zhange et al (2017) COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level. Biochem.Biophys.Res.Commun. 493 85 PMID: 28919423

Majolée et al (2019) CSN5 inhibition triggers inflammatory signaling and Rho/ROCK-dependent loss of endothelial integrity. Sci.Rep. 9 9131 PMID: 31148579

If you know of a relevant reference for CSN5i-3, please let us know.

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Keywords: CSN5i-3, CSN5i-3 supplier, CSN5I3, potent, selective, inhibitors, inhibits, CSN5, COP9, signalosome, antitumour, antitumor, constitutive, photomorphogenesis, 9, NEDD8, neddylation, cullin-ring, CRL, Rho, GTPases, expression, activation, activators, Ubiquitin, E3, Ligases, 7089, Tocris Bioscience

Citations for CSN5i-3

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Literature in this Area

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