Eganelisib (IPI-549)

Name: Eganelisib (IPI-549)
Brand: Selleck Chemicals
SKU: S8330
Rating: 5 (10 reviews)

For research use only.

Catalog No.S8330

10 publications

CAS No. 1693758-51-8

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.

Selleck's Eganelisib (IPI-549) has been cited by 10 publications

Exp Mol Med, 2020, 22

PubMed: 32444799 ( click the link to review the publication )

Cancer Sci, 2020, 10.1111/cas.14616

PubMed: 32798273 ( click the link to review the publication )

Eur J Immunol, 2020, 8

PubMed: 32383488 ( click the link to review the publication )

Int Immunopharmacol, 2020, 82:106342

PubMed: 32143003 ( click the link to review the publication )

Int J Radiat Oncol Biol Phys, 2020, 10.1016/j.ijrobp.2020.01.030

PubMed: 32036006 ( click the link to review the publication )

Nat Commun, 2020, 11(1):3521

PubMed: 32665556 ( click the link to review the publication )

Nat Commun, 2019, 10(1):1515

PubMed: 30944303 ( click the link to review the publication )

J Exp Clin Cancer Res, 2019, 14;38(1):191

PubMed: 31088502 ( click the link to review the publication )

Nat Commun, 2018, 9(1):873

PubMed: 29491374 ( click the link to review the publication )

J Biol Chem, 2018, 293(36):14022-14039

PubMed: 30018141 ( click the link to review the publication )

Purity & Quality Control

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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].

Assay

Methods	Test Index	PMID
Western blot	p-AKT / AKT / p-p65 / p65 ; PubMed: 27642729 Nature 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.	27642729

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

Cell Research:

^[1]

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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:

^[1]

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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)

References

[1] Evans CA, et al. ACS Med Chem Lett. 2016, 7(9):862-7.

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 Download Eganelisib (IPI-549) SDF

Molecular Weight	528.56
Formula	C₃₀H₂₄N₈O₂
CAS No.	1693758-51-8
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC(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

In vivo Formulation Calculator (Clear solution)

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% DMSO+ % + % Tween 80+ % ddH₂O

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Working concentration： mg/ml；

Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

Molarity Calculator

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The Serial Dilution Calculator Equation

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Molecular Weight Calculator

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Tech Support

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.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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PI3K Signaling Pathway Map

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Eganelisib (IPI-549)