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|
GNE-317 is a potent, brain-penetrant PI3K inhibitor.
Serabelisib (INK-1117,MLN-1117,TAK-117) is a potent and selective oral PI3Kα isoform inhibitor (IC50 of 21 nmol/L against PI3Kα) that has demonstrated > 100-fold selectivity relative to other class I PI3K family members (PI3Kβ/γ/δ) and mTOR, and a high degree of selectivity against many other kinase.
SF2523 is a highly selective and potent inhibitor of PI3K with IC50 values of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.
IPI549 is a potent and selective PI3Kγ Inhibitor with IC50 of 16 nM.
Vps34-IN1 is a potent and highly selective Vps34 inhibitor with IC50 of 25 nM invitro,which does not significantly inhibit the isoforms of class I as well as class II PI3Ks.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.