IC-87114

371242-69-2

C22H19N7O

DMSO : 10 mg/mL (25.16 mM; Need ultrasonic)

PI3K/Akt/mTOR

IC-87114 is a potent and selective PI3Kdelta inhibitor with IC₅₀ of 0.5 uM. IC50 & Target: IC50: 0.5 uM (PI3Kdelta)^[1] In Vitro: IC-87114 (IC87114), an analog of the original inhibitor, is synthesized and tested for PI3Kdelta selectivity relative to the other class I PI3Ks. The IC₅₀ of IC87114 for PI3Kdelta inhibition is 0.5 uM whereas the IC₅₀ values for PI3Kalpha, PI3Kbeta, and PI3Kgamma are >100, 75, and 29 uM, respectively. Thus IC87114 is 58-fold more selective for PI3Kdelta relative to PI3Kgamma, and over 100-fold selective relative to PI3Kalpha and PI3Kbeta. IC87114 selectively antagonizes PI3Kdelta over at least a concentration range of 0.3-10 uM^[1]. IC-87114 (10 uM) is also used to selectively inhibit PI3Kdelta catalytic activity to address this question. IC87114 (10 uM) 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-alpha (10 ng/mL; P<0.001) and TNF-alpha (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 uM) and TNF-alpha (0-20 ng/mL) than only treatment with TNF-alpha (0-20 ng/mL; n=5; P<0.01). IC87114 (10 uM) also effectively inhibits p110delta catalytic activities (Akt phosphorylation) in macrophages with or without TNF-alpha treatment for 24 hours (n=6; P<0.001)^[2]. In Vivo: 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^[3].