Nemiralisib hydrochloride
Based on 1 Customer Validation
Nemiralisib hydrochloride (GSK2269557) is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9.
For research use only. We do not sell to patients.
- Purity : 98.86%
- CAS No.: 1254036-77-5
- Formula: C26H29ClN6O
- Molecular Weight:477.00
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Storage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
PI3Kδ 9.9 (pKi) |
PI3Kγ 5.2 (pIC50) |
PI3Kα 5.3 (pIC50) |
PI3Kβ 5.8 (pIC50) |
In Vitro
Nemiralisib hydrochloride is highly selective for PI3Kδ, with >1000-fold selectivity over the closely related isoforms PI3Kα (pIC50=5.3), PI3Kβ (pIC50=5.8) and PI3Kγ (pIC50=5.2). Nemiralisib hydrochloride inhibits IFNγ in the peripheral blood mononuclear (PBMC) assay with an pIC50 of 9.7[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.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1254036-77-5
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Appearance Solid
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Molecular Weight 477.00
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Formula C26H29ClN6O
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Color Light yellow to yellow
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SMILES
[H]Cl.CC(N1CCN(CC2=CN=C(C3=CC(C4=CC=CC5=C4C=CN5)=CC6=C3C=NN6)O2)CC1)C
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Synonyms
GSK2269557
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
DMSO : 16.67 mg/mL (34.95 mM; ultrasonic and warming and heat to 60°C; 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 (sealed storage, away from moisture). 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 (sealed storage, away from moisture). 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: ≥ 1.67 mg/mL (3.50 mM); Clear solution
This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 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: ≥ 1.67 mg/mL (3.50 mM); Clear solution
This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 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. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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.
Protocol
Kinase Assay[1]
Inhibition of PI3Kinase enzymatic activity is determined using a homogeneous time resolved fluorescence (HTRF) kit assay format. Reactions are performed in assay buffer containing 50 mM HEPES, pH 7.0, 150 mM NaCl, 10 mM MgCl2, <1 % cholate (w/v), <1 % CHAPS (w/v), 0.05 % sodium azide (w/v) and 1 mM DTT. Enzymes are preincubated with compound, serially diluted 4-fold in 100 % DMSO, for 15 mins prior to reaction initiation upon addition of substrate solution containing ATP at Km for the specific isoform tested (PI3Kα at 250 μM, PI3Kβ at 400 μM, PI3Kδ at 80 μM and PI3Kγ at 15 μM), PIP2 at either 5 μM (PI3Kδ) or 8 μM (PI3Kα, PI3Kβ and PI3Kγ) and 10 nM biotin-PIP3. Assays are quenched after 60 mins by addition of a quench/detection solution prepared in 50 mM HEPES pH 7.0, 150 mM NaCl, <1 % cholate, <1 % Tween 20, 30 mM EDTA, 40 mM potassium fluoride and 1 mM DTT containing 16.5 nM GRP-1 PH domain, 8.3 nM Streptavidin-APC and 2 nM Europium-anti-GST, and are left for a further 60 mins in the dark to equilibrate prior to reading using a BMG RubyStar plate reader. Ratio data are normalised to high (no compound) and low (no enzyme) controls prior to fitting using a logistical four parameter equation to determine IC50[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration[1]
Rats[1]
In vivo pharmacokinetics is tested in Sprague Dawley male rats. Compounds (e.g., GSK2269557) are administered discretely by the oral or intravenous routes, at a dose level of 3 and 1 mg/kg respectively (n=2 rats/route). Compounds (e.g., GSK2269557) are formulated as a solution in DMSO:PEG200:water (5:45:50 v/v/v) at a dose volume of 6 (oral) and 2 (intravenous) mL/kg. All animals are serially bled from the tail vein and blood samples collected over a time-course of 0-7 h are submitted to LC-MS/MS analysis for the quantification of the parent compound. The main pharmacokinetic parameters are estimated by non-compartmental analysis.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (279 KB)
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SDS (418 KB)
- English - EN (418 KB)
- Français - FR (418 KB)
- Deutsch - DE (418 KB)
- Norwegian - NO (418 KB)
- Español - ES (418 KB)
- Swedish - SV (418 KB)
- Italian - IT (418 KB)
- Korean - KR (418 KB)
- Portuguese - PT (418 KB)
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Handling Instructions (2659 KB)
References
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 (sealed storage, away from moisture). 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 | 2.0964 mL | 10.4822 mL | 20.9644 mL | 52.4109 mL |
| 5 mM | 0.4193 mL | 2.0964 mL | 4.1929 mL | 10.4822 mL | |
| 10 mM | 0.2096 mL | 1.0482 mL | 2.0964 mL | 5.2411 mL | |
| 15 mM | 0.1398 mL | 0.6988 mL | 1.3976 mL | 3.4941 mL | |
| 20 mM | 0.1048 mL | 0.5241 mL | 1.0482 mL | 2.6205 mL | |
| 25 mM | 0.0839 mL | 0.4193 mL | 0.8386 mL | 2.0964 mL | |
| 30 mM | 0.0699 mL | 0.3494 mL | 0.6988 mL | 1.7470 mL |
Nemiralisib hydrochloride Related Classifications
HY-19535 Related Classifications
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