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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Nemiralisib targets phosphoinositide 3-kinase delta (PI3Kδ), a class I PI3K isoform predominantly expressed in leukocytes. PI3Kδ plays a critical role in B cell receptor, T cell receptor, and Fc receptor signaling. By selectively inhibiting PI3Kδ, Nemiralisib modulates immune cell activation, proliferation, and survival. The compound shows high selectivity for PI3Kδ over other PI3K isoforms, particularly PI3Kγ. This selectivity is important for minimizing off-target effects.
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| ln Vitro |
The extremely selective PI3Kδ is more than 1000 times more likely to be targeted by nemiralisib (GSK2269557 free base) than the closely related isoforms PI3Kα (pIC50=5.3), PI3Kβ (pIC50=5.8), and PI3Kγ (pIC50=5.2). In peripheral blood mononuclear (PBMC) assays, nemalisib suppresses IFNγ with a pIC50 of 9.7 [1].
In vitro, Nemiralisib potently inhibits PI3Kδ with a pKi of 9.9. It shows >10,000-fold selectivity for PI3Kδ over PI3Kγ (pKi 5.2). The compound is a potent and highly selective PI3Kδ inhibitor. It has been characterized in biochemical and cellular assays. Detailed in vitro data are available in the primary literature. The compound is a valuable tool for studying PI3Kδ function in immune cells. |
| ln Vivo |
In order to assess the suitability of this product series for inhalation administration clearance in rat microsomes, Sprague Dawley male rats were used to collect in vivo pharmacokinetic data. Nemiralisib, for example, was given intravenously or orally to two rats per route, with doses of 3 mg/kg and 1 mg/kg, respectively. In the disease-associated brown Norway rat acute OVA model of type 2 helper T cell (Th2)-driven lung inflammation, nemalisib free base is effective [1].
In vivo, Nemiralisib has been developed for inhaled delivery for the treatment of respiratory diseases. It is a potent and highly selective PI3Kδ inhibitor. The compound's inhaled delivery route enables direct targeting of lung inflammation. Further in vivo studies are needed to fully characterize its efficacy and safety profile. The compound is a research tool for respiratory disease research. |
| Enzyme Assay |
In vitro kinase assays for Nemiralisib typically use recombinant PI3Kδ enzyme and phosphatidylinositol substrate. The compound is dissolved in DMSO and diluted in assay buffer. Reactions are initiated by adding ATP and incubated at room temperature for 30-60 minutes. Phosphatidylinositol 3-phosphate production is detected by AlphaScreen, TR-FRET, or radiometric methods. pKi and IC₅₀ values are calculated from dose-response curves. Selectivity is assessed against other PI3K isoforms (α, β, γ) and a panel of kinases.
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| Cell Assay |
For cell-based assays, immune cell lines (e.g., B cells, T cells) are cultured in RPMI-1640 with 10% FBS. Cells are seeded in 96-well plates and treated with Nemiralisib at various concentrations (0.001-10 μM) for 1-24 hours. Cells are stimulated with anti-IgM (B cells) or anti-CD3/CD28 (T cells). PI3Kδ-dependent signaling (e.g., Akt phosphorylation) is assessed by Western blotting or phospho-flow cytometry. Cell proliferation is assessed by [³H]-thymidine incorporation or CFSE dilution. Cytokine production is measured by ELISA. All treatments include vehicle controls and are performed in triplicate.
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| Animal Protocol |
In vivo, Nemiralisib is typically administered via inhalation. The compound is formulated for aerosol delivery. For respiratory disease models (e.g., asthma, COPD), animals are dosed by inhalation at various regimens. Endpoints include airway inflammation, lung function, and cytokine levels in bronchoalveolar lavage fluid. Blood and tissue samples are collected for pharmacokinetic and pharmacodynamic analysis. All procedures follow institutional animal care guidelines.
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| ADME/Pharmacokinetics |
Nemiralisib 2HCl (MW 440.54, C₂₆H₂₈N₈O) is a PI3Kδ inhibitor with a pKi of 9.9. The compound shows selectivity for PI3Kδ over PI3Kγ. It is soluble in DMSO. Detailed pharmacokinetic parameters are available from preclinical studies. The compound is designed for inhaled delivery. It is typically stored at -20°C. The compound is for research purposes.
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| Toxicity/Toxicokinetics |
Toxicology data for Nemiralisib are limited in publicly available sources. As a PI3Kδ inhibitor, potential effects on immune function should be considered. The compound is for research use only and not intended for human therapeutic applications. Standard safety pharmacology and toxicology studies would be required for therapeutic development. The compound should be handled with standard laboratory safety precautions.
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| References | |
| Additional Infomation |
Nemiralisib is being investigated in clinical trial NCT03345407 (a dose-exploration study of Nemiralisib (GSK2269557) in patients with acute moderate or severe exacerbations of chronic obstructive pulmonary disease (COPD).
See also: Gsk-2269557 (note moved to). Nemiralisib (GSK2269557) is a research-grade PI3Kδ inhibitor for studying immune cell signaling and respiratory diseases. Its primary applications include immunology, respiratory disease research, and drug discovery. The compound is not approved for clinical use and has not entered clinical trials. It is commercially available from various chemical suppliers for research purposes only. Its mechanism involves selective inhibition of PI3Kδ, modulating immune cell activation and function. |
| Molecular Formula |
C26H28N6O
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|---|---|
| Molecular Weight |
440.540124893188
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| Exact Mass |
440.232
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| CAS # |
1254036-71-9
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| Related CAS # |
Nemiralisib hydrochloride;1254036-77-5
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| PubChem CID |
49784002
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| Appearance |
White to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
706.2±70.0 °C at 760 mmHg
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| Flash Point |
380.9±35.7 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.686
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| LogP |
3.23
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
655
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| Defined Atom Stereocenter Count |
0
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| SMILES |
0
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~75.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.25 mg/mL (5.11 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2699 mL | 11.3497 mL | 22.6994 mL | |
| 5 mM | 0.4540 mL | 2.2699 mL | 4.5399 mL | |
| 10 mM | 0.2270 mL | 1.1350 mL | 2.2699 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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