CSN5i-3 |
رقم الكتالوجGC34340
One-Click Copy Product Info
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CSN5i-3 هو مثبط فعال وانتقائي ومتاح عن طريق الفم لـ CSN5 / Jab1 ، ويثبط تجلط Cul1 المحفز بواسطة CSN بقيمة IC50 تبلغ 5.8 نانومتر.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2375740-98-8
Sample solution is provided at 25 µL, 10mM.
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CSN5i-3 is a novel, potent, highly selective, and orally bioavailable small molecule inhibitor that targets the CSN5/Jab1 (COPS5) protein—a key protein hydrolytic subunit of the COP9 signaling complex. CSN5i-3 exhibits extremely high inhibitory activity against this target, with an IC50 value of 5.8nM[1, 2]. The core function of CSN5 is to cleave the NEDD8 modification from the Cullin-RING E3 ubiquitin ligase. CSN5i-3 can potently inhibit this de-Neddase activity of CSN5, thereby interfering with the normal function of the CRL ubiquitin ligase[3].
In vitro, treatment of human breast cancer BT474 and SKBR3 cells with CSN5i-3 (2µM) for 24h significantly induced apoptosis and G1 phase cell cycle arrest, and increased the levels of the apoptosis marker cleaved PARP and the cell cycle-related protein p27[4]. Treatment of human umbilical vein endothelial cells (HUVECs) with CSN5i-3 (1, 4µM) for 5h induced a significant weakening of endothelial barrier function, induced the expression of RhoGTPase RhoB in endothelial cells, and formed actin stress fibers[5].
In vivo, subcutaneous injection of CSN5i-3 (10mg/kg) into MDA-MB-231 cell xenograft mice for 18 days inhibited tumor growth in mice, and combined treatment with Talazoparib significantly enhanced the antitumor efficacy[6].
References:
[1] Schlierf A, Altmann E, Quancard J, et al. Targeted inhibition of the COP9 signalosome for treatment of cancer[J]. Nature communications, 2016, 7(1): 13166.
[2] Yin L, Xue Y, Shang Q, et al. Pharmaceutical inhibition of neddylation as promising treatments for various cancers[J]. Current Topics in Medicinal Chemistry, 2019, 19(12): 1059-1069.
[3] Wu J T, Chan Y R, Chien C T. Protection of cullin–RING E3 ligases by CSN–UBP12[J]. Trends in cell biology, 2006, 16(7): 362-369.
[4] Xiao H, Claret F X, Shen Q. The novel Jab1 inhibitor CSN5i-3 suppresses cell proliferation and induces apoptosis in human breast cancer cells[J]. Neoplasma, 2019, 66(3).
[5] Majolée J, Pronk M C A, Jim K K, et al. CSN5 inhibition triggers inflammatory signaling and Rho/ROCK-dependent loss of endothelial integrity[J]. Scientific reports, 2019, 9(1): 8131.
[6] Peng X, Wang Y, Yu Z, et al. Jab1 regulates HRR mRNA stability to modulate PARP inhibitor sensitivity in triple-negative breast cancer[J]. Molecular Cancer, 2025, 24(1): 217.
| Cell experiment [1]: | |
Cell lines | BT474、SKBR3 cells |
Preparation Method | BT474 and SKBR3 cells were seeded in a 6-well plate. After exposure to 2µM CSN5i-3 for 24h, cells were stained with Annexin V-FlTC and analyzed by FACSCalibur to assess the apoptotic cell percentages. |
Reaction Conditions | 2µM; 24h |
Applications | Jab1 inhibitor CSN5i-3 can significantly induce apoptosis in BT474 and SKBR3 cells. |
| Animal experiment [2]: | |
Animal models | BALB/c nude mice |
Preparation Method | MDA-MB-231 cells were subcutaneously injected into the right flanks of 4- to 5‐week‐old female BALB/c nude mice. When tumors reached 1000mm3, they were excised, diced into 2mm×2mm×2mm pieces, and implanted into the right flanks of BALB/c nude mice. Tumors were allowed to grow to 100mm3 before random assignment into four groups (n=5): vehicle, CSN5i-3 (10mg/kg), Talazoparib (0.33mg/kg), or a combination of CSN5i-3 and Talazoparib. Tumor size was measured every 3 days. On day 19, mice were euthanized, and tumors were harvested. Tumors were either formalin-fixed or paraffin-embedded for histological analysis. |
Dosage form | 10mg/kg; 18 days; s.c. |
Applications | Combined treatment with CSN5i-3 and Talazoparib significantly enhanced antitumor efficacy. |
References: | |
| Cas No. | 2375740-98-8 | SDF | |
| Canonical SMILES | O=C(C1=CC(C(F)F)=NN1C(C)C)NC2=CC(C3=CC=CC=C3)=C([C@@H]4N5C(CCC[C@@H]4O)=CN=C5)C=C2 | ||
| Formula | C28H29F2N5O2 | M.Wt | 505.56 |
| الذوبان | DMSO: ≥ 100 mg/mL (197.80 mM) | Storage | Store at -20°C, protect from light, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.978 mL | 9.89 mL | 19.78 mL |
| 5 mM | 395.6 μL | 1.978 mL | 3.956 mL |
| 10 mM | 197.8 μL | 989 μL | 1.978 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 23 reference(s) in Google Scholar.)