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Chemical Structure| 2375740-98-8 Chemical Structure| 2375740-98-8

Structure of CSN5i-3
CAS No.: 2375740-98-8

Chemical Structure| 2375740-98-8

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CSN5i-3 is a selective, orally available CSN5/Jab1 inhibitor that effectively inhibits CSN-mediated Cul1 deneddylation with an IC50 value of 5.8 nM, widely used in research on cell signaling regulation.

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Product Details of CSN5i-3

CAS No. :2375740-98-8
Formula : C28H29F2N5O2
M.W : 505.56
SMILES Code : O=C(C1=CC(C(F)F)=NN1C(C)C)NC2=CC(C3=CC=CC=C3)=C([C@H]4[C@@H](O)CCCC5=CN=CN54)C=C2
MDL No. :MFCD31657416

Safety of CSN5i-3

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
PC3 cells 10μM 72 h Inhibition of CSN5 attenuated PC3 invasiveness by repressing EMT markers Oncogene. 2022 Jan;41(5):671-682
22RV1 cells 5μM 3 days Inhibition of CSN5 suppressed AR signaling by directly inhibiting both AR and AR-V7 proteins Oncogene. 2022 Jan;41(5):671-682
LNCaP cells 5μM 3 days Inhibition of CSN5 suppressed AR signaling by directly inhibiting both AR and AR-V7 proteins Oncogene. 2022 Jan;41(5):671-682
143B osteosarcoma sarcospheres 2.9 μM 48 h CSN5i-3 significantly inhibits the growth of osteosarcoma sarcospheres Oncogene. 2020 Jun;39(23):4581-4591
hFOB cells 6.6 μM 48 h CSN5i-3 inhibits hFOB cell growth but less effectively than osteosarcoma cells Oncogene. 2020 Jun;39(23):4581-4591
143B osteosarcoma cells 3.5 μM 48 h CSN5i-3 inhibits osteosarcoma cell growth and reduces cell viability Oncogene. 2020 Jun;39(23):4581-4591
hCMEC/D3 cells 1 μM 4 h Investigation of the effect of CSN5i-3 on CUL1 NEDDylation in hCMEC/D3 cells, showing that CSN5i-3 almost completely blocked the deNEDDylation activity of the CSN. Cell Mol Life Sci. 2023 Aug 19;80(9):262
BV2 microglia 1 μM 4 h Investigation of the effect of CSN5i-3 on CUL1 NEDDylation in BV2 microglia, showing that CSN5i-3 increased NEDDylated CUL1 levels. Cell Mol Life Sci. 2023 Aug 19;80(9):262
HEK293T cells 1 μM or 4 μM 5 h To assess the effect of CSN5i-3 on RhoB ubiquitination, results showed that CSN5i-3 treatment did not significantly alter the ubiquitination state of RhoB. Sci Rep. 2019 May 31;9(1):8131
Human Umbilical Vein Endothelial Cells (HUVECs) 1 μM or 4 μM 5 h To evaluate the effect of CSN5i-3 on endothelial barrier function, results showed that CSN5i-3 significantly reduced endothelial barrier function and increased macromolecular permeability. Sci Rep. 2019 May 31;9(1):8131
293T cells 50 nM To determine the half maximal effective concentration (EC50) of CSN5i-3 in 293T cells, results showed an EC50 of approximately 50 nM. Proc Natl Acad Sci U S A. 2022 Sep 6;119(36):e2205608119
K562 cells 1 μM 4 h To evaluate the effect of CSN5i-3 on NEDD8 modification of cullin proteins in K562 cells, results showed that CSN5i-3 promoted the accumulation of NEDD8-conjugated cullins. Proc Natl Acad Sci U S A. 2022 Sep 6;119(36):e2205608119
SU-DHL-1 0.013 μM Induction of apoptosis, reduction in Fbxo7 levels Nat Commun. 2016 Oct 24;7:13166
HCT116 1 μM 16 h Inhibition of CSN5 activity, leading to blocked Cul1 deneddylation and Skp2 degradation Nat Commun. 2016 Oct 24;7:13166

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOG-SCID male mice C4–2 xenograft model Oral gavage 150 mg/kg Twice daily for 31 days CSN5i-3 significantly inhibited tumor growth, reducing tumor volume from 1342.9 mm3 to 18.85 mm3 Oncogene. 2022 Jan;41(5):671-682
Zebrafish (Danio rerio) Tg(Fli1:GFP)y1 casper zebrafish embryos Added to the swimming water 50 μM 48-72 hours To evaluate the effect of CSN5i-3 on vascular permeability in zebrafish embryos, results showed that CSN5i-3 significantly increased vascular permeability. Sci Rep. 2019 May 31;9(1):8131

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.98mL

0.40mL

0.20mL

9.89mL

1.98mL

0.99mL

19.78mL

3.96mL

1.98mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
 

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