Size | Price | Stock | Qty |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
Targets |
PI3Kδ (pKi = 9.9 nM); PI3Kγ (pIC50 = 5.2 nM); PI3Kα (pIC50 = 5.3 nM); PI3Kβ (pIC50 = 5.8 nM)
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ln Vitro |
Nemiralisib (GSK2269557 free base) 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 inhibits IFNγ with a pIC50 of 9.7 in the peripheral blood mononuclear (PBMC) assay[1].
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ln Vivo |
To assess the suitability of the series for inhaled delivery clearance data in rat microsomes and subsequently in vivo pharmacokinetic data from Sprague Dawley male rats is obtained. Compounds (e.g., Nemiralisib) are administered via the oral or intravenous routes at dose levels of 3 and 1 mg/kg, respectively (n=2 rats/route). Nemiralisib free base is effective in a disease-relevant brown norway rat acute OVA model of Type 2 helper T-cells (Th2)-driven lung inflammation[1].
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Enzyme Assay |
Nemiralisib (GSK2269557 free base) 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 inhibits IFNγ in the peripheral blood mononuclear (PBMC) assay with an pIC50of 9.7.
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Animal Protocol |
Rats: In vivo pharmacokinetics is tested in Sprague Dawley male rats. Compounds (e.g., Nemiralisib) are discretely administered via the oral or intravenous routes, at dose levels of 3 and 1 mg/kg, respectively (n = 2 rats/route). Nemiralisib is one of the compounds that is 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. Blood samples collected over a time course of 0–7 h are serially drawn from each animal's tail vein, and the parent compound's concentration is determined using LC–MS/MS analysis. Analyses without compartments are used to estimate the primary pharmacokinetic parameters.
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References |
Molecular Formula |
C26H28N6O
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Molecular Weight |
440.540124893188
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Exact Mass |
440.2325
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Elemental Analysis |
C, 70.89; H, 6.41; N, 19.08; O, 3.63
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CAS # |
1254036-71-9
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Related CAS # |
Nemiralisib hydrochloride;1254036-77-5
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Appearance |
Solid powder
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SMILES |
CC(C)N1CCN(CC1)CC2=CN=C(O2)C3=C4C=NNC4=CC(=C3)C5=C6C=CNC6=CC=C5
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InChi Key |
MCIDWGZGWVSZMK-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C26H28N6O/c1-17(2)32-10-8-31(9-11-32)16-19-14-28-26(33-19)22-12-18(13-25-23(22)15-29-30-25)20-4-3-5-24-21(20)6-7-27-24/h3-7,12-15,17,27H,8-11,16H2,1-2H3,(H,29,30)
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Chemical Name |
2-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole
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Synonyms |
GSK-2269557; GSK 2269557; GSK2269557; Nemiralisib HCl; Nemiralisib hydrochloride
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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:~88 mg/mL (~199.8 mM)
Water: <1 mg/mL Ethanol: ~8 mg/mL (~18.2 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.
NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT03398421 | Completed | Drug: Nemiralisib Drug: Itraconazole |
Pulmonary Disease, Chronic Obstructive |
GlaxoSmithKline | January 17, 2018 | Phase 1 |
NCT02593539 | Completed | Drug: Nemiralisib | Activated PI3K-delta Syndrome | GlaxoSmithKline | July 22, 2016 | Phase 2 |