GSK3117391
Based on 1 Customer Validation
GSK3117391 (ESM-HDAC391; CHR-5154; HDAC-IN-3) is an orally active HDAC inhibitor with a IC50 of 55 nM. Using esterase-sensitive motif technology, GSK3117391 is selectively converted into its active acid metabolite HDAC189 in cells expressing carboxylesterase-1. GSK3117391 induces sustained global protein acetylation in monocytes, inhibits the production of proinflammatory cytokines, depletes circulating monocytes, downregulates the expression of CSF1R, and inhibits monocyte adhesion and differentiation. GSK3117391 can be used in the research of chronic inflammatory diseases.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.40%
- No. CAS: 1018673-42-1
- Fòrmula: C22H33N3O4
- Peso molecular:403.52
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
Descripciòn
IC50 & Target
[1]|
HDAC 55 nM (IC50) |
In Vitro
GSK3117391 potently inhibits class I, class IIb, and class IV HDAC enzymes, and shows no activity against class IIa HDAC enzymes[1].
GSK3117391 (1.5 nM-10 μM; 4 h) selectively increases global protein acetylation levels in human blood monocytes, with an EC50 of 158 nM, while exerting minimal effects on lymphocytes and granulocytes[1].
GSK3117391 (1.5 nM-10 μM; overnight) inhibits the production of TNF-α in human whole blood stimulated by LPS (HY-D1056), with an IC50 of 174 nM[1].
GSK3117391 (10 μM; 1-6 h) rapidly converts to its acidic metabolite HDAC189 in human CD14+ monocytes, and the concentration of HDAC189 increases continuously within 6 hours of incubation[1].
GSK3117391 (0.01 nM-100 μM; 1-8 h) induces time- and concentration-dependent downregulation of CSF1R expression on human CD14+ monocytes without affecting CCR2 expression[1].
GSK3117391 (0.51 nM-10 μM; 4-48 h) inhibits M-CSF-induced differentiation of human CD14+ monocytes, with an IC50 value of 118 nM after 4 h of incubation and 19 nM after 20 h of incubation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CES1/Es1elo (human CES1 expressed under CD68 promoter on low plasma esterase Es1elo background; male; age-matched)[1]
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Dosage:3 mg/kg (single dose); 10 mg/kg (single dose; two doses 24 hours apart)
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Administration:i.p.; single dose; two doses 24 hours apart
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Result:Caused a 78% reduction in total circulating monocytes at 6 hours post-dose, with recovery by 24 hours (10 mg/kg single dose).
Caused an 84% reduction in circulating monocytes at 30 hours post-initial dose (10 mg/kg two doses 24 hours apart).
Reduced classical Ly6Chi monocytes by 72%, intermediate Ly6Cint monocytes by 81%, and non-classical Ly6Clo monocytes by 90% at 6 hours post-10 mg/kg dose.
Caused a 59% reduction in total circulating monocytes at 6 hours post-dose (3 mg/kg single dose).
Reduced CD115 expression on remaining circulating monocytes by 59% at 6 hours post-3 mg/kg dose.
Reduced CD115 expression on remaining circulating monocytes by 33% at 6 hours post-10 mg/kg dose.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 1018673-42-1
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Appearance Solid
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Peso molecular 403.52
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Fòrmula C22H33N3O4
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Color Light yellow to khaki
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SMILES
O=C([C@@H](NCC1=CN=C(CCC(NO)=O)C=C1)C2CCCCC2)OC3CCCC3
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Synonyms
ESM-HDAC391; CHR-5154; HDAC-IN-3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvente y solubilidad
In Vitro:
DMSO : 50 mg/mL (123.91 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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 (6.20 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.20 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 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%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
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Ficha de datos (273 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.4782 mL | 12.3910 mL | 24.7819 mL | 61.9548 mL |
| 5 mM | 0.4956 mL | 2.4782 mL | 4.9564 mL | 12.3910 mL | |
| 10 mM | 0.2478 mL | 1.2391 mL | 2.4782 mL | 6.1955 mL | |
| 15 mM | 0.1652 mL | 0.8261 mL | 1.6521 mL | 4.1303 mL | |
| 20 mM | 0.1239 mL | 0.6195 mL | 1.2391 mL | 3.0977 mL | |
| 25 mM | 0.0991 mL | 0.4956 mL | 0.9913 mL | 2.4782 mL | |
| 30 mM | 0.0826 mL | 0.4130 mL | 0.8261 mL | 2.0652 mL | |
| 40 mM | 0.0620 mL | 0.3098 mL | 0.6195 mL | 1.5489 mL | |
| 50 mM | 0.0496 mL | 0.2478 mL | 0.4956 mL | 1.2391 mL | |
| 60 mM | 0.0413 mL | 0.2065 mL | 0.4130 mL | 1.0326 mL | |
| 80 mM | 0.0310 mL | 0.1549 mL | 0.3098 mL | 0.7744 mL | |
| 100 mM | 0.0248 mL | 0.1239 mL | 0.2478 mL | 0.6195 mL |
GSK3117391 Related Classifications
HY-19772 Related Classifications
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