Eganelisib (IPI-549)

Catalog No.S8330 Batch:S833003

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Technical Data

Formula

C30H24N8O2
Molecular Weight 528.56 CAS No. 1693758-51-8
Solubility (25°C)* In vitro DMSO 100 mg/mL (189.19 mM)
Water ˂1 mg/mL
Ethanol ˂1 mg/mL
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Eganelisib (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.
Targets
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].
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].

Protocol (from reference)

Cell Assay:

[1]
  • 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.
Animal Study:

[1]
  • 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.

Selleck's Eganelisib (IPI-549) has been cited by 22 publications

Combination Treatment Targeting mTOR and MAPK Pathways Has Synergistic Activity in Multiple Myeloma [ Cancers (Basel), 2023, 15(8)2373] PubMed: 37190302
Pan-PI3K inhibition with copanlisib overcomes Treg- and M2-TAM-mediated immune suppression and promotes anti-tumor immune responses [ Clin Exp Med, 2023, 10.1007/s10238-023-01227-6] PubMed: 37935952
Inactivation of TRPM7 Kinase Targets AKT Signaling and Cyclooxygenase-2 Expression in Human CML Cells [ Function (Oxf), 2023, 4(6):zqad053] PubMed: 37786778
Targetable leukemia dependency on noncanonical PI3Kγ signaling [ bioRxiv, 2023, 10.1101/2023.12.15.571909] PubMed: none
Mechanical checkpoint regulates monocyte differentiation in fibrotic niches [ Nat Mater, 2022, 21(8):939-950] PubMed: 35817965
P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia [ Nat Cancer, 2022, 3(7):837-851] PubMed: 35668193
Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3Kγ inhibitor can enhance immunogenicity and eradicate tumors [ J Immunother Cancer, 2022, 10(2)e003564] PubMed: 35217574
DKK1 Promotes Tumor Immune Evasion and Impedes Anti-PD-1 Treatment by Inducing Immunosuppressive Macrophages in Gastric Cancer [ Cancer Immunol Res, 2022, 10(12):1506-1524] PubMed: 36206576
The efficacy of PI3Kγ and EGFR inhibitors on the suppression of the characteristics of cancer stem cells [ Sci Rep, 2022, 12(1):347] PubMed: 35013447
Therapeutic inhibition of the SRC-kinase HCK facilitates T cell tumor infiltration and improves response to immunotherapy [ Sci Adv, 2022, 8(25):eabl7882] PubMed: 35731867

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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