HD-TAC7
Based on 1 Customer Validation
HD-TAC7 is a selective HDAC3 PROTAC degrader with an IC50 of 1.1 μM. By recruiting the CRBN E3 ligase, HD-TAC7 induces ubiquitin-proteasome degradation and selective downregulation of HDAC3, which in turn increases H3K27 acetylation levels and downregulates the NF-κB subunit p65, exerting anti-inflammatory activity. HD-TAC7 is used in research on COVID-19, SARS-CoV-2 infection, asthma, chronic obstructive pulmonary disease, and colon cancer.
(Pink: HDAC3 ligand (HY-184951); Blue: Cereblon ligand (HY-10984); Black: linker).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 98.53%
- CAS 番号: 2978763-95-8
- 分子式: C33H32FN7O7
- 分子量:657.65
-
保管条件: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]
-
生物活性
-
化学情報
-
溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
-
Help & FAQs
PROTACs アイソフォーム固有の製品をすべて表示
More
生物活性
製品説明
IC50 & Target
[1]|
HDAC3 0.32 μM (DC50) |
HDAC3 1.1 μM (IC50) |
HDAC1 3.6 μM (IC50) |
HDAC2 4.2 μM (IC50) |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| RAW264.7 | DC50 |
0.32 μM
|
HDAC3 degradation activity against mouse RAW 264.7 macrophages assessed via Western blot.
HDAC3 degradation activity against mouse RAW 264.7 macrophages assessed via Western blot.
|
36841549 |
体外実験
HD-TAC7 (0.4-100 μM) does not reduce the viability of RAW264.7 macrophages[2].
HD-TAC7 (10 μM; 24 h) downregulates the level of NF-κB p65 protein in RAW 264.7 macrophages[1].
HD-TAC7 (0.001-30 μM) induces concentration-dependent degradation of HDAC3 protein in RAW264.7 macrophages without altering the protein levels of HDAC1 or HDAC2[2].
HD-TAC7 (10 μM; 24 h) induces time-dependent degradation of HDAC3 protein in RAW264.7 macrophages[2].
HD-TAC7 (10 μM; 24 h) increases the acetylation level of lysine 27 on histone 3 in RAW264.7 macrophages[2].
HD-TAC7 (10 μM; 24 h) reduces the level of nuclear NF-κB p65 protein in RAW264.7 macrophages[2].
HD-TAC7 (10 μM; 24 h)-induced HDAC3 degradation in RAW264.7 macrophages is inhibited by pretreatment with Pomalidomide (HY-10984), whereas pretreatment with Tacedinaline (CI994) (HY-50934) does not interfere with this activity[2].
HD-TAC7 (10 μM; 24 h)-induced HDAC3 degradation in RAW264.7 macrophages is inhibited by co-treatment with a proteasome inhibitor, indicating that this degradation process is proteasome-dependent[2].
HD-TAC7 exhibits selective inhibitory activity against HDAC3, which is more potent than its effects on HDAC1 and HDAC2, with an IC50 of 1.1 μM for HDAC3[1].
HD-TAC7 (0.01-10 μM; 2-48 h) selectively degrades HDAC3 in RAW 264.7 macrophages, with a DC50 of 0.32 μM. HD-TAC7 achieves maximal degradation within 6 h, and this effect persists for at least 48 h, while it does not alter the levels of HDAC1 and HDAC2[1].
HD-TAC7 (10 μM; 24 h) increases the acetylation level of H3K27 in RAW 264.7 macrophages[1].
HD-TAC7 (10 μM; 24 h) mediates proteasome- and CRBN-dependent degradation of HDAC3 in RAW 264.7 macrophages, as evidenced by the reversal of this degradation upon co-treatment with immunomodulatory imide drugs, class I histone deacetylase inhibitors, or proteasome inhibitors[1].
HD-TAC7 (1-10 μM; 24 h) exerts no significant effect on the transcription of pro-inflammatory or anti-inflammatory genes (TNFα, IL-6, iNOS, IL-10) in RAW 264.7 macrophages stimulated with Lipopolysaccharides, from E. coli O111:B4 (LPS) (HY-D1056A1)/IFNγ when treated at 1 μM or 10 μM for 24 h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:RAW264.7 macrophages
-
Concentration:10 μM
-
Incubation Time:2, 4, 6, 24, 48 h
-
Result:Led to a time-dependent reduction in HDAC3 protein levels, with visible decreases starting at 2 h and progressive reduction through 48 h of incubation.
-
Cell Line:RAW264.7 macrophages
-
Concentration:10 μM
-
Incubation Time:24 h
-
Result:Increased the acetylation level of H3K27, as indicated by elevated acH3K27 signal relative to the DMSO control.\nReduced the level of nuclear NF-κB p65 protein relative to the DMSO control.
-
Cell Line:RAW264.7 macrophages
-
Concentration:10 μM
-
Incubation Time:24 h (HD-TAC7 incubation); 1 h pre-treatment + 24 h co-incubation or 25 h alone (pomalidomide/CI994)
-
Result:Induced HDAC3 degradation when used alone.
Had its HDAC3 degradation effect blocked by pre-treatment with pomalidomide.
Had its HDAC3 degradation effect unaffected by pre-treatment with CI994.
-
Cell Line:RAW264.7 macrophages
-
Concentration:10 μM HD-TAC7
-
Incubation Time:24 h
-
Result:Reduced HDAC3 protein levels when used alone.
Had its HDAC3 degradation effect blocked by co-treatment with proteasome inhibitor.
-
Cell Line:RAW 264.7 macrophages
-
Concentration:0.01, 0.1, 1, 10 μM (concentration-dependent testing); 10 μM (time-dependent testing)
-
Incubation Time:24 h (concentration-dependent testing); 2, 4, 6, 24, 48 h (time-dependent testing)
-
Result:Mediated concentration-dependent degradation of HDAC3 with a DC50 of 0.32 μM.
Showed no significant degradation of HDAC1 or HDAC2 at any tested concentration.
Reached maximum HDAC3 degradation at 6 h, which persisted for at least 48 h.
-
Cell Line:RAW 264.7 macrophages
-
Concentration:10 μM
-
Incubation Time:24 h
-
Result:Induced an increase in H3K27 acetylation levels compared to untreated control cells.
-
Cell Line:RAW 264.7 macrophages
-
Concentration:10 μM
-
Incubation Time:24 h (HD-TAC7 treatment); 1 h (pre-treatment prior to HD-TAC7 addition); 24 h (proteasome inhibitor co-treatment)
-
Result:Rescued HDAC3 degradation with co-treatment of immunomodulatory imide drug or class I histone deacetylase inhibitor, confirming dependence on CRBN and HDAC binding.
Completely blocked HDAC3 degradation with co-treatment of proteasome inhibitor, confirming dependence on proteasome activity.
-
Cell Line:LPS/IFNγ-stimulated RAW 264.7 macrophages
-
Concentration:1, 10 μM
-
Incubation Time:24 h, with LPS/IFNγ stimulation for the final 4 h
-
Result:Did not significantly alter transcription levels of pro-inflammatory genes TNFα, IL-6, and iNOS.
Did not significantly alter transcription levels of anti-inflammatory gene IL-10.
Showed different effects compared to HDAC inhibitors Entinostat and CI994 which upregulated these genes.
-
Cell Line:RAW 264.7 macrophages
-
Concentration:10 μM
-
Incubation Time:24 h, with LPS/IFNγ stimulation for the final 4 h
-
Result:Downregulated NF-κB p65 protein levels, similar to the effect of pomalidomide treatment.
化学情報
-
CAS 番号 2978763-95-8
-
性状 Solid
-
分子量 657.65
-
分子式 C33H32FN7O7
-
Color Light yellow to green yellow
-
SMILES
NC1=CC(F)=CC=C1NC(C2=CC=C(C=C2)NC(CCCCNC(CNC3=C4C(N(C(C4=CC=C3)=O)C5CCC(NC5=O)=O)=O)=O)=O)=O
-
輸送条件
Room temperature in continental US; may vary elsewhere.
-
保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
体外:
DMSO : 100 mg/mL (152.06 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.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
体内:
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: ≥ 2.63 mg/mL (4.00 mM); Clear solution
This protocol yields a clear solution of ≥ 2.63 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (26.3 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.
純度とドキュメンテーション
-
データシート (291 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)
-
取扱説明書 (2659 KB)
参考文献
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 | 1.5206 mL | 7.6028 mL | 15.2057 mL | 38.0141 mL |
| 5 mM | 0.3041 mL | 1.5206 mL | 3.0411 mL | 7.6028 mL | |
| 10 mM | 0.1521 mL | 0.7603 mL | 1.5206 mL | 3.8014 mL | |
| 15 mM | 0.1014 mL | 0.5069 mL | 1.0137 mL | 2.5343 mL | |
| 20 mM | 0.0760 mL | 0.3801 mL | 0.7603 mL | 1.9007 mL | |
| 25 mM | 0.0608 mL | 0.3041 mL | 0.6082 mL | 1.5206 mL | |
| 30 mM | 0.0507 mL | 0.2534 mL | 0.5069 mL | 1.2671 mL | |
| 40 mM | 0.0380 mL | 0.1901 mL | 0.3801 mL | 0.9504 mL | |
| 50 mM | 0.0304 mL | 0.1521 mL | 0.3041 mL | 0.7603 mL | |
| 60 mM | 0.0253 mL | 0.1267 mL | 0.2534 mL | 0.6336 mL | |
| 80 mM | 0.0190 mL | 0.0950 mL | 0.1901 mL | 0.4752 mL | |
| 100 mM | 0.0152 mL | 0.0760 mL | 0.1521 mL | 0.3801 mL |
HD-TAC7 関連分類
HY-146346 関連分類
Powered by Bioz