Nemiralisib (GSK2269557)

Alias: GSK-2269557; GSK 2269557; GSK2269557; Nemiralisib HCl; Nemiralisib hydrochloride
Cat No.:V2539 Purity: ≥98%
Nemiralisib (GSK-2269557) is a novel, potent and selective PI3Kδ inhibitor with pKi of 9.9.
Nemiralisib (GSK2269557) Chemical Structure CAS No.: 1254036-71-9
Product category: PI3K
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
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Other Forms of Nemiralisib (GSK2269557):

  • Nemiralisib HCl
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description
Nemiralisib (GSK-2269557) is a novel, potent and selective PI3Kδ inhibitor that is potent and selective, with a pKi of 9.9. It works in an acute OVA model of lung inflammation driven by Th2 that is relevant to the disease in brown Norway rats. Since leukocytes are a significant source of PI3Kδ, it is a desirable target for the treatment of inflammatory conditions like asthma,6 chronic obstructive pulmonary disease (COPD), and autoimmune diseases. For the treatment of respiratory conditions like asthma and COPD, GSK-2269557 is currently undergoing clinical trials.
Biological Activity I Assay Protocols (From Reference)
Targets
PI3Kδ (pKi = 9.9 nM); PI3Kγ (pIC50 = 5.2 nM); PI3Kα (pIC50 = 5.3 nM); PI3Kβ (pIC50 = 5.8 nM)
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].
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].
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.
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.
References

[1]. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem. 2015 Sep 24;58(18):7381-99.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C26H28N6O
Molecular Weight
440.540124893188
Exact Mass
440.2325
Elemental Analysis
C, 70.89; H, 6.41; N, 19.08; O, 3.63
CAS #
1254036-71-9
Appearance
Solid powder
SMILES
CC(C)N1CCN(CC1)CC2=CN=C(O2)C3=C4C=NNC4=CC(=C3)C5=C6C=CNC6=CC=C5
InChi Key
MCIDWGZGWVSZMK-UHFFFAOYSA-N
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)
Chemical Name
2-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole
Synonyms
GSK-2269557; GSK 2269557; GSK2269557; Nemiralisib HCl; Nemiralisib hydrochloride
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO:~88 mg/mL (~199.8 mM)
Water: <1 mg/mL
Ethanol: ~8 mg/mL (~18.2 mM)
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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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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.
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Clinical Trial Information
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
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