IC-87114

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的选择性 PI3Kδ 抑制剂，IC50 为 0.5 uM。

A potent and selective PI3Kδ inhibitor with IC50 of 0.5 uM; displays 58-fold selectivity over PI3Kγ, and >100-fold over PI3Kα and PI3Kβ; inhibits polarized morphology of neutrophils, fMLP-stimulated PIP3 production and chemotaxis; inhibits constitutive phosphorylation of Akt/PKB and suppresses AML cell proliferation; reduces vascular permeability in a murine model of asthma.

IC-87114 (IC87114), an analog of the original inhibitor, is synthesized and tested for PI3Kδ selectivity relative to the other class I PI3Ks. The IC50 of IC87114 for PI3Kδ inhibition is 0.5 μM whereas the IC50 values for PI3Kα, PI3Kβ, and PI3Kγ are >100, 75, and 29 μM, respectively. Thus IC87114 is 58-fold more selective for PI3Kδ relative to PI3Kγ, and over 100-fold selective relative to PI3Kα and PI3Kβ. IC87114 selectively antagonizes PI3Kδ over at least a concentration range of 0.3-10 μM. IC-87114 (10 μM) is also used to selectively inhibit PI3Kδ catalytic activity to address this question. IC87114 (10 μM) effectively inactivates Akt in macrophages after treatment for 1 hour (n=6; P<0.001 versus control). The effect of IC-87114 (IC87114) is next detected ton AP-1 DNA-binding activity. The electrophoretic mobility shift assay assay demonstrates that DNA-binding activity of AP-1 is significantly increased after the treatment with TNF-α (10 ng/mL; P<0.001) and TNF-α (20 ng/mL; P<0.001). IC87114 alone induces AP-1 DNA-binding activity after treatment for 1 hour. Furthermore, there is stronger AP-1 DNA-binding activity after costimulation of IC87114 (10 μM) and TNF-α (0-20 ng/mL) than only treatment with TNF-α (0-20 ng/mL; n=5; P<0.01). IC87114 (10 μM) also effectively inhibits p110δ catalytic activities (Akt phosphorylation) in macrophages with or without TNF-α treatment for 24 hours (n=6; P<0.001).

Treatment with PD 89059 (10?mg/kg), IC-87114 (0.3?mg/kg) and BAY 11-7085 (10?mg/kg), significantly (P<0.05) reduces the OVA- induced inflammatory cell influx into the airways and the histopathological airway remodeling. However, these treatments does not significantly improve OVA induced-AHR (P>0.05). Of note, the observed reduction in the histopathological airway remodeling induced by PD 89059, IC-87114 and BAY 11-7085 are less effective as compared to the reduction seen with AG 1478 and SU6656.

IC87114 | IC 87114

PI3K/Akt/mTOR signaling

PI3K

PI3Kβ|PI3Kγ|PI3Kδ

Cancer

——

371242-69-2

397.4326

C22H19N7O

>98% (HPLC)

10 mM in DMSO

O=C1N(C2=CC=CC=C2C)C(CN3C=NC4=C(N)N=CN=C34)=NC5=C1C(C)=CC=C5

4(3H)-Quinazolinone, 2-[(6-amino-9H-purin-9-yl)methyl]-5-methyl-3-(2-methylphenyl)-

(-20℃)

With Ice Pack

≥ 2 years