IC87114 (PIK-293) is the first isoform-selective PI3K inhibitor. This quinazolinone purine inhibits p110δ (IC50=0.13µM) at mid-nanomolar concentrations and shows 100-1000-fold selectivity over other class I PI3Ks (p110α, p110β and p110γ ). The selectivity of IC87114 is remarkable given that the residues that line the ATP binding pocket of the class I PI3Ks are highly conserved. IC87114 down-regulated p-Akt and p-FOXO3a, reduced proliferation and induced apoptosis in AML primary cells overexpressing p110δ PI3K. Inhibition of PI3K delta with IC87114 blocked both fMLP- and TNF1 alpha-induced neutrophil superoxide generation and elastase exocytosis. The PI3K delta inhibitor IC87114 also blocked TNF1 alpha-stimulated elastase exocytosis from neutrophils in a mouse model of inflammation.
| Cell Experiment | |
|---|---|
| Cell lines | human neutrophil |
| Preparation method | Measurement of neutrophil adhesion and migration The adhesion assays were performed by the following modifications of the procedure described by Sadhu et al. Briefly, 96-well plates were coated overnight with 5 μg/ml ICAM-1/Ig, blocked with 1% HSA (no. 12666; Calbiochem, La Jolla, CA) in RPMI 1640, and 2 × 105 neutrophils (untreated or pretreated with the indicated concentration of IC87114) were added in triplicate wells. After incubation at 37°C for the desired time, 5% CO2 glutaraldehyde was added to a 1% final concentration. Unbound cells were removed by washing the wells in water and the adherent cells were stained with crystal violet. Cell adhesion was quantified by reading the intensity of crystal violet on Spectra MAX (Molecular Devices, Sunnyvale, CA) at 570 nm. |
| Concentrations | 1 μ M |
| Incubation time | 3 h |
| Animal Experiment | |
|---|---|
| Animal models | WT B6 and p110δD910A Mice |
| Formulation | 1% methylcellulose (MCL) |
| Dosages | 30 mg/kg once |
| Administration | orally |
| Molecular Weight | 397.43 |
| Formula | C22H19N7O |
| CAS Number | 371242-69-2 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
| Related PI3K Products |
|---|
| SNV4818
SNV4818 is a potential best-in-class (best-in-class) mutation-selective PI3K-α inhibitor with excellent selectivity for the H1047X mutant and moderate selectivity for the related E545/542X mutant. |
| hSMG-1 inhibitor 11j
hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC50 of 0.11 nM. |
| RLY-2608
RLY-2608 is a first-in-class, orally active, selective inhibitor of PI3Ka metabolism. |
| EDI048
EDI048 is an orally active Cryptosporidium PI4K inhibitor for the research of cryptosporidiosis. |
| PI3Kδ-IN-13
PI3Kδ-IN-13 is a PI3Kδ inhibitor (IC50=2.6 nM). |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
