SZU-B6
Based on 1 Customer Validation
SZU-B6 is an orally active SIRT6 PROTAC degrader with DC50 values of 45 nM in SK-HEP-1 cells and 154 nM in Huh-7 cells, respectively. SZU-B6 mediates proteasome-dependent degradation of SIRT6 by recruiting the CRBN E3 ubiquitin ligase. SZU-B6 impairs DNA damage repair and promotes radiosensitization of cancer cells. SZU-B6 induces cell cycle arrest and apoptosis in cancer cells. SZU-B6 inhibits the proliferation of liver cancer cells. SZU-B6 suppresses the tumor growth of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in mice. SZU-B6 can be used in research related to hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
(Pink: SIRT6 ligand (HY-16605); Blue: Cereblon E3 ligase ligand; Black: linker (HY-W012935)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.78%
- No. CAS: 3059333-98-8
- Fòrmula: C29H32FN7O6
- Peso molecular:593.61
-
Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Actividad biológica
-
Chemical Information
-
Solvente y solubilidad
- Pureza y Documentación
- Referencias
-
Help & FAQs
Ver todos los productos específicos de isoformas PROTACs
More
Actividad biológica
Descripciòn
IC50 & Target
[1]|
SIRT6 |
In Vitro
SZU-B6 (200-2000 nM; 36 h) induces dose-dependent degradation of SIRT6 in SK-HEP-1 cells. After 36 h of treatment, the degradation rate reaches 67.7% at 200 nM and 92.5% at 2 μM[1].
SZU-B6 (0-10 μM; 36 h) potently induces dose-dependent degradation of SIRT6 in Huh-7 cells, with a DC50 of 154.28 nM and a maximum degradation efficiency of 91.79%[1].
SZU-B6 (0.02-5 μM; 24-36 h) induces time- and dose-dependent selective degradation of SIRT6 in SK-HEP-1, Huh-7 and Hep3B cells[1].
SZU-B6 (2.5 μM; 36 h with 2 h pretreatment) induces SIRT6 degradation in SK-HEP-1 cells via a CRBN- and proteasome-dependent mechanism[1].
SZU-B6 (0-10 μM; 72 h) potently inhibits the proliferation of SK-HEP-1 cells with an IC50 of 1.51 μM; when combined with 3 Gy irradiation, its antiproliferative activity is significantly enhanced, with an IC50 of 0.45 μM after 72 h of treatment[1].
SZU-B6 (2.5 μM) inhibits colony formation in SK-HEP-1 and Huh-7 cells[1].
SZU-B6 (0.04-5 μM; 36 h) induces dose-dependent degradation of SIRT6 in SK-HEP-1 cells and impairs DNA damage repair function[1].
SZU-B6 (5 μM; administered 36 h prior to transfection) significantly inhibits the homologous recombination DNA double-strand break repair pathway in DR-U2OS cells and the non-homologous end joining DNA double-strand break repair pathway in EJ5-U2OS cells, respectively[1].
SZU-B6 (5 μM; administered 36 h prior to 10 Gy irradiation) increases residual DNA damage in SK-HEP-1 cells after 10 Gy irradiation, as evidenced by longer comet tail moments following pretreatment with 5 μM for 36 h[1].
SZU-B6 (0-10 μM; 72 h) induces dose-dependent G2/M phase arrest and apoptosis in SK-HEP-1 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:SK-HEP-1, Huh-7, and Hep3B HCC cells
-
Concentration:0.02, 0.2, 1, 2.5, 5 μM (36 h); 1 μM (time-course)
-
Incubation Time:36 h; 24 h, 36 h (time-course)
-
Result:Induced near-complete SIRT6 degradation (≥98%) in SK-HEP-1 cells at 5 μM after 36 h.
Induced degradation in SK-HEP-1 cells as early as 24 h, reaching a plateau at 36 h.
Induced dose-dependent SIRT6 degradation in Huh-7 cells, with a visible hook effect at 5 μM after 36 h.
Induced SIRT6 degradation in Hep3B cells, with a plateau at 36 h after 1 μM treatment.
Left SIRT1 and SIRT7 protein levels unaffected in SK-HEP-1 and Huh-7 cells.
-
Cell Line:SK-HEP-1 HCC cells
-
Concentration:0-10 μM (alone); 0-10 μM plus 3 Gy irradiation
-
Incubation Time:72 h
-
Result:Inhibited SK-HEP-1 cell proliferation with an IC50 of 1.51 μM when used alone.
Exhibited enhanced antiproliferative activity with an IC50 of 0.45 μM when combined with 3 Gy irradiation.
-
Cell Line:SK-HEP-1 HCC cells
-
Concentration:0, 2.5, 5, 10 μM (alone); 2.5 μM plus 2 μM Sorafenib; 2.5 μM plus 1 μM Camptothecin; 2.5 μM plus 3 Gy irradiation
-
Incubation Time:72 h
-
Result:Induced dose-dependent G2/M phase arrest in SK-HEP-1 cells when used alone.
Induced dose-dependent apoptosis in SK-HEP-1 cells, with up to 60% apoptotic cells at 10 μM after 72 h when used alone.
Significantly increased apoptosis levels when combined with Sorafenib compared to treatment alone.
Significantly increased apoptosis levels when combined with Camptothecin (HY-16560) compared to treatment alone.
Significantly increased apoptosis levels when combined with irradiation compared to treatment alone.
-
Cell Line:SK-HEP-1 HCC cells
-
Concentration:0.04, 0.2, 1, 5 μM (36 h); 2.5 μM (prior to DNA-damaging agent exposure)
-
Incubation Time:36 h; 36 h prior to DNA-damaging agent exposure
-
Result:Induced dose-dependent reduction of SIRT6 fluorescence in SK-HEP-1 cells after 36 h.
Impaired γ-H2AX foci formation in response to DNA-damaging agents, indicating reduced DNA damage repair capacity.
In Vivo
SZU-B6 (10 mg/kg; p.o.; 18 days) significantly inhibits tumor growth of intrahepatic cholangiocarcinoma in mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BALB/c nude (6-8 weeks of age; subcutaneous xenograft model with SK-HEP-1 cells)[1]
-
Dosage:10 mg/kg
-
Administration:every other day; 4 weeks
-
Result:Achieved a relative tumor volume growth rate (T/C ratio) of 39.6%.
Caused no body weight loss.
Degraded SIRT6 protein in tumor tissue.
Reduced SIRT6 levels, increased γ-H2AX (indicating DNA damage), and increased cleaved caspase 3 (indicating apoptosis) in treated tumors.
Showed no significant pathological damage in heart, liver, spleen, lung, and kidney.
-
Animal Model:C57BL/6 mice (intrahepatic cholangiocarcinoma induced via hydrodynamic tail vein injection of AKT/YAP/SB plasmids)[2]
-
Dosage:10 mg/kg
-
Administration:i.g.; 18 days
-
Result:Significantly suppressed ICC tumour growth, as evidenced by reduced liver weight and liver-to-body weight ratio compared to vehicle controls.
Chemical Information
-
No. CAS 3059333-98-8
-
Appearance Solid
-
Peso molecular 593.61
-
Fòrmula C29H32FN7O6
-
Color Light yellow to yellow
-
SMILES
NC1=C([N+]([O-])=O)C=CC(N2CCN(CC3CCN(C4=CC5=C(C(N(C6C(NC(CC6)=O)=O)C5=O)=O)C=C4F)CC3)CC2)=C1
-
Envío
Room temperature in continental US; may vary elsewhere.
-
Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (168.46 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
-
Ficha de datos (281 KB)
-
SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
-
Instrucciones de manejo (2659 KB)
Referencias
[1]. Huang J, et al. Discovery of Novel PROTAC SIRT6 Degraders with Potent Efficacy against Hepatocellular Carcinoma. Journal of medicinal chemistry. 2024 Oct 10;67(19):17319-17349. [Content Brief]
[2]. Zhang M, et al. SIRT6 promotes intrahepatic cholangiocarcinoma development by reprogramming glutamine metabolism via enhanced GLUL. Gut. 2026 Jun 09;75(7):1383-1396. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.6846 mL | 8.4230 mL | 16.8461 mL | 42.1152 mL |
| 5 mM | 0.3369 mL | 1.6846 mL | 3.3692 mL | 8.4230 mL | |
| 10 mM | 0.1685 mL | 0.8423 mL | 1.6846 mL | 4.2115 mL | |
| 15 mM | 0.1123 mL | 0.5615 mL | 1.1231 mL | 2.8077 mL | |
| 20 mM | 0.0842 mL | 0.4212 mL | 0.8423 mL | 2.1058 mL | |
| 25 mM | 0.0674 mL | 0.3369 mL | 0.6738 mL | 1.6846 mL | |
| 30 mM | 0.0562 mL | 0.2808 mL | 0.5615 mL | 1.4038 mL | |
| 40 mM | 0.0421 mL | 0.2106 mL | 0.4212 mL | 1.0529 mL | |
| 50 mM | 0.0337 mL | 0.1685 mL | 0.3369 mL | 0.8423 mL | |
| 60 mM | 0.0281 mL | 0.1404 mL | 0.2808 mL | 0.7019 mL | |
| 80 mM | 0.0211 mL | 0.1053 mL | 0.2106 mL | 0.5264 mL | |
| 100 mM | 0.0168 mL | 0.0842 mL | 0.1685 mL | 0.4212 mL |
SZU-B6 Related Classifications
HY-168574 Related Classifications
Powered by Bioz