SH6
Based on 1 Customer Validation
SH6 is a CRBN-dependent proteasome degrader that targets ZBTB7A. SH6 can be used in the research of sickle cell disease and β-thalassemia.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.43%
- No. CAS: 2619408-35-2
- Fòrmula: C23H23ClN4O4
- Peso molecular:454.91
-
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
Actividad biológica
Descripciòn
IC50 & Target
[1]|
ZBTB7A |
In Vitro
SH6 binds specifically to ZBTB7A via two predicted sites, with the primary site between zinc fingers 1 and 2 relying on residues R402, Y410, and Q422 for stable interaction, as supported by docking scores of -7.12 for the primary site[1].
SH6 (0.25-5 μM; 6–24 h) reduces the ZBTB7A protein level in differentiating HUDEP-2 cells in a concentration-dependent manner[1].
SH6 (50 μM; 24 h) reduces ZBTB7A protein levels in SNU398 cells via post-transcriptional mechanisms, with a 4.1-fold decrease in protein abundance and a compensatory 7-fold increase in mRNA levels[1].
SH6 (0.25-5 μM; 24 h-4 days) mediates CRBN- and proteasome-dependent degradation of ZBTB7A in wild-type HUDEP-2 cells, with dose-dependent reduction in protein levels and compensatory increases in mRNA, while having no effect on ZBTB7A levels in CRBN-knockout cells[1].
SH6 (0.25 μM; 4 days or 11 days) induces CRBN- and ZBTB7A-dependent HbF expression in wild-type HUDEP-2 cells, increasing HbF to 19% of total hemoglobin and HBG1/2 mRNA 6.1-fold, while having no effect on HbF levels in CRBN-knockout or ZBTB7A-knockout cells[1].
SH6 (0.05 μM; intermittent incubation from day 7 to harvest) induces HbF expression in healthy donor-derived CD34+ HSPC-derived erythroid cells, reduces ZBTB7A protein levels, and does not impair erythroid differentiation or enucleation[1].
SH6 (0.01-0.1 μM; incubation during differentiation) induces dose-dependent HbF expression in SCD patient-derived CD34+ HSPC-derived erythroid cells, increasing HbF to 15.0% of total hemoglobin at 0.05 μM, reducing HBB/HBBS mRNA levels, and not impairing erythroid differentiation or enucleation[1].
SH6 (0.05-0.1 μM; incubation during differentiation) induces HbF expression in β-thalassemia patient-derived CD34+ HSPC-derived erythroid cells, increasing HbF to 43.8% of total hemoglobin at 0.05 μM, with a trend of dose-dependent induction[1].
SH6 (10-100 nM; 72 h) has a favorable toxicity profile in hESCs and hiPSCs at concentrations up to 100 nM, as measured by MTT cell viability assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:differentiating HUDEP-2 cells
-
Concentration:2 μM; 0.25-5 μM
-
Incubation Time:6 h; 12 h; 24 h
-
Result:Reduced the ZBTB7A protein level in differentiating HUDEP-2 cells.
-
Cell Line:wild-type HUDEP-2 cells、CRBN-knockout cells
-
Concentration:0.25 μM; 5 μM
-
Incubation Time:24 h
-
Result:Mediated CRBN- and proteasome-dependent ZBTB7A degradation in wild-type HUDEP-2 cells.
Had no effect on ZBTB7A levels in CRBN knockout cells.
-
Cell Line:human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs)
-
Concentration:10-100 nM
-
Incubation Time:72 h
-
Result:Exhibited favorable viability profiles in hESCs and hiPSCs at the tested concentrations, with viability expressed as a percentage of vehicle control.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:NOD.Cg-KitW-41J Tyr + Prkdcˢᶜⁱᵈ Il2rgᵗᵐ1Wʲˡ/ThomJ (NBSGW) (6-8 weeks of age; immunodeficient, conditioned with low-dose Busulfan (HY-B0245) for human CD34+ hematopoietic stem and progenitor cell engraftment)[1]
-
Dosage:2.5 mg/kg; 5 mg/kg
-
Administration:i.p.; daily; 3 weeks
-
Result:Induced HbF to 4.0% in human CD235a-selected bone marrow erythroid cells at 5 mg/kg.
Caused dose-dependent reduction of ZBTB7A protein levels in human CD235a+ bone marrow cells, with greater reduction observed at the 5 mg/kg dose compared to the 2.5 mg/kg dose.
Maintained human bone marrow hCD45 engraftment, multilineage hematopoietic reconstitution (T cells, B cells, myeloid cells), and erythroid maturation markers (CD235a, CD36, CD71) comparable to vehicle controls.
Exhibited no significant treatment-related adverse effects, including stable body weight, normal serum chemistry (urea nitrogen, creatinine, albumin, AST, ALT), normal complete blood count parameters, and no changes in organ weights or tissue architecture.
Chemical Information
-
No. CAS 2619408-35-2
-
Appearance Solid
-
Peso molecular 454.91
-
Fòrmula C23H23ClN4O4
-
Color White to yellow
-
SMILES
O=C(NC1=C(N)C=C(Cl)C=C1)/C=C/C2=C(NC3=CC(OC)=C(OC)C(OC)=C3)N=CC=C2
-
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 (219.82 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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.50 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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 (288 KB)
-
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
-
Instrucciones de manejo (2659 KB)
Referencias
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 | 2.1982 mL | 10.9912 mL | 21.9824 mL | 54.9559 mL |
| 5 mM | 0.4396 mL | 2.1982 mL | 4.3965 mL | 10.9912 mL | |
| 10 mM | 0.2198 mL | 1.0991 mL | 2.1982 mL | 5.4956 mL | |
| 15 mM | 0.1465 mL | 0.7327 mL | 1.4655 mL | 3.6637 mL | |
| 20 mM | 0.1099 mL | 0.5496 mL | 1.0991 mL | 2.7478 mL | |
| 25 mM | 0.0879 mL | 0.4396 mL | 0.8793 mL | 2.1982 mL | |
| 30 mM | 0.0733 mL | 0.3664 mL | 0.7327 mL | 1.8319 mL | |
| 40 mM | 0.0550 mL | 0.2748 mL | 0.5496 mL | 1.3739 mL | |
| 50 mM | 0.0440 mL | 0.2198 mL | 0.4396 mL | 1.0991 mL | |
| 60 mM | 0.0366 mL | 0.1832 mL | 0.3664 mL | 0.9159 mL | |
| 80 mM | 0.0275 mL | 0.1374 mL | 0.2748 mL | 0.6869 mL | |
| 100 mM | 0.0220 mL | 0.1099 mL | 0.2198 mL | 0.5496 mL |
SH6 Related Classifications
HY-178486 Related Classifications
Powered by Bioz