1. PI3K/Akt/mTOR
  2. PI3K

GSK2269557 free base (Synonyms: Nemiralisib)

Cat. No.: HY-19535A Purity: 99.09%
Handling Instructions

GSK2269557 free base is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9.

For research use only. We do not sell to patients.
GSK2269557 free base Chemical Structure

GSK2269557 free base Chemical Structure

CAS No. : 1254036-71-9

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 140 In-stock
1 mg USD 84 In-stock
5 mg USD 144 In-stock
10 mg USD 228 In-stock
25 mg USD 492 In-stock
50 mg USD 852 In-stock
100 mg USD 1440 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

GSK2269557 free base is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9.

IC50 & Target[1]

PI3Kδ

9.9 (pKi)

PI3Kγ

5.2 (pIC50)

PI3Kα

5.3 (pIC50)

PI3Kβ

5.8 (pIC50)

In Vitro

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). GSK2269557 free base inhibits IFNγ in the peripheral blood mononuclear (PBMC) assay with an pIC50 of 9.7[1].

In 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., GSK2269557) are administered by the oral or intravenous routes, at a dose level of 3 and 1mg/kg respectively (n=2 rats/route). GSK2269557 free base is active in a disease relevant brown norway rat acute OVA model of Type 2 helper T-cells (Th2)-driven lung inflammation[1].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 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
Please refer to the solubility information to select the appropriate solvent.
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].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

GSK2269557 free base is formulated as a solution in DMSO:PEG200:water (5:45:50 v/v/v) (Rats)[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.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

440.54

Formula

C₂₆H₂₈N₆O

CAS No.

1254036-71-9

SMILES

CC(N1CCN(CC2=CN=C(C3=CC(C4=CC=CC5=C4C=CN5)=CC6=C3C=NN6)O2)CC1)C

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 31 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
GSK2269557 free base
Cat. No.:
HY-19535A
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