GSK-2269557 has low oral bioavailability (F=2%) and in vivo clearance of 28 mL/min/kg but has a high volume of distribution of 6.3 L/kg. GSK-2269557 induces concentration-dependent increases in QT interval and Tp-e at 0.3 and 1 μM (1 and 0.5 Hz) and an increase in QRS at 1 μM (2 Hz), however, no treatment-related torsades de pointes (TdP) arrhythmias are observed. In a disease relevant brown Norway rat acute OVA model of Th2 driven lung inflammation, GSK-2269557 is shown to protect against eosinophil recruitment with an ED50 of 67 μg/kg and dose-dependently reduces recruitment of all leukocyte subpopulations and IL-13 in the lungs.
|Animal models||Sprague Dawley male rats|
|Formulation||DMSO/PEG200/water (5:45:50 v/v/v)|
|Dosages||3 mg/kg; IV:1 mg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||88 mg/mL in DMSO|
Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease.
Down K, et al. J Med Chem. 2015 Sep 24;58(18):7381-99. PMID: 26301626.
|Related PI3K Products|
LY3023414 is a selective ATP-competitive inhibitor of PI3Kα and mTOR, DNA-PK, and other class I PI3K family members.
SAR405 is a PIK3C3/Vps34 inhibitor with an IC50 of 1.2 nM. SAR405 also is a proximal inhibitor of the autophagy machinery.
Tenalisib (RP6530) is a potent and selective dual PI3Kδ/γ inhibitor with IC50 values of 24.5 nM and 33.2 nM for PI3Kδ and PI3Kγ, respectively. Its selectivity over α and β isoforms are more than 300-fold and 100-fold, respectively.
PI 828 is a pI 3-kinase inhibitor, more potent than LY 294002.
IPI-3063 is a potent and selective p110δ inhibitor with biochemical IC50 of 2.5 ± 1.2 nM and IC50 values for the other class I PI3K isoforms (p110α, p110β, p110γ) are at least 400-fold higher.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.