For research use only.

Catalog No.S8330

8 publications

IPI-549 Chemical Structure

Molecular Weight(MW): 528.56

IPI-549 is a potent inhibitor of PI3K-γ with >100-fold selectivity over other lipid and protein kinases. The biochemical IC50 for PI3K-γ is 16 nM.

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Biological Activity

Description IPI-549 is a potent inhibitor of PI3K-γ with >100-fold selectivity over other lipid and protein kinases. The biochemical IC50 for PI3K-γ is 16 nM.
PI3Kγ [1]
(Cell-free assay)
16 nM
In vitro

IPI-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. In vitro, 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)[1].

Methods Test Index PMID
Western blot
p-AKT / AKT / p-p65 / p65 ; 

PubMed: 27642729     

Immunoblotting to detect pThr308Akt, total Akt, phospho-p65 and total p65 in LPS and IL-4 stimulated, macrophages that were treated with vehicle or the PI3Kγ inhibitor IPI-549.

In vivo In 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[1].


Cell Research:


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  • Cell lines: SKOV-3 cells
  • Concentrations: --
  • Incubation Time: 30 min
  • Method:

    SKOV-3 cells are seeded into 96-well cell culture-grade plates at a density of 200,000 cells/200 μL/well of RPMI-1640 with 10% FBS. Cells are incubated overnight at 5% CO2 and 37 °C. Compounds are added to the cells, resulting in a final DMSO concentration of 0.5%, and incubated for 30 minutes at 5% CO2 and 37 °C. Media is then aspirated and 50 μL/well of ice-cold lysis buffer is added. Plates are incubated on ice for 5 minutes and then centrifuged at 3000 rpm at 4 °C for 5 minutes.

    (Only for Reference)
Animal Research:


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  • Animal Models: CD-1 mice, Sprague-Dawley rats, beagle dogs and cynomolgus monkeys.
  • Dosages: 0.5-1.25 mg/mL(For PO dosing); 5-10 mg/mL(for efficacy studies); 0.25-0.4 mg/mL(for IV dosing)
  • Administration: p.o.; i.v.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (189.19 mM)
Ethanol 8 mg/mL (15.13 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 528.56


CAS No. 1693758-51-8
Storage powder
in solvent
Synonyms N/A
Smiles CC(NC(=O)C1=C2N=CC=C[N]2N=C1N)C3=CC4=CC=CC(=C4C(=O)N3C5=CC=CC=C5)C#CC6=C[N](C)N=C6

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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PI3K Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID