Eganelisib (IPI-549) (C09-0880-922)

InformationEganelisib (IPI-549) is a potent inhibitor ofPI3K-γwith >100-fold selectivity over other lipid and protein kinases. The biochemicalIC50for PI3K-γ is 16 nM.TargetsPI3Kγ (Cell-free assay) 16 nMIn vitroIPI-549 is found to be a remarkably tight binder to PI3K-γ with a Kd of 290 pM and >58-fold weaker affinity for other Class I PI3K isoforms. It does not significantly inhibit a panel of 468 mutant and nonmutant protein and lipid kinases (including Class II PI3K isoforms) at 1 μM. In PI3K-α, -β, -γ, and -δ dependent cellular phospho-AKT assays, IPI-549 demonstrates excellent PI3K-γ potency (IC50 = 1.2 nM) and selectivity against other Class I PI3K isoforms (>146-fold). Furthermore, IPI-549 dose dependently inhibits PI3K-γ-dependent bone marrow-derived macrophage (BMDM) migration in vitro. IPI-549 is also found to be selective against a panel of 80 GPCRs, ion channels, and transporters at 10 μM. IPI-549 shows moderate to high cell permeability across Caco-2 cell monolayers, is slowly metabolized in cultured hepatocytes (t1/2 > 360 min), and demonstrates IC50s greater than 20 μM for the CYP isoforms tested (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4).In vivoIn vivo (mice, rats, dog, and monkeys), IPI-549 has excellent oral bioavailability, low clearance, and distributes into tissues with a mean volume of distribution of 1.2 L/kg. It has a favorable pharmacokinetic profile to allow potent and selective inhibition of PI3K-γ in vivo. IPI-549 can significantly reduce neutrophil migration in a dose-dependent manner in mouse model when administered orally at all of the tested doses. In addition, IPI-54 has been shown to inhibit tumor growth in murine syngeneic models through alteration of immune cells in the tumor microenvironment.Cell Research(from reference)Cell lines：SKOV-3 cells Incubation Time：30 min. Specification: 0.97 Molecular Formula: C30H24N8O2 Molecular Weight: 528.56 PubChem CID: 91933883 Isomeric SMILES: C[C@@H](C1=CC2=C(C(=CC=C2)C#CC3=CN(N=C3)C)C(=O)N1C4=CC=CC=C4)NC(=O)C5=C6N=CC=CN6N=C5N Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/E413975-SCI_10ab454d500964d409160ddfa04ea463.pdf