Name: Eganelisib (IPI-549)
Brand: Selleck Chemicals
SKU: S8330
Rating: 5 (29 reviews)

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Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.98%

99.98

Verwandte Ziele	Akt mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Weitere PI3K Inhibitoren	GDC-0077 (Inavolisib) SAR405 Quercetin (Sophoretin) LY294002 XL147 analogue Tersolisib (STX-478) Buparlisib (BKM120) 740 Y-P (PDGFR 740Y-P) GO-203 TFA Paxalisib (GDC-0084)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien	Assay-Typ	Inkubationszeit	Aktivitätsbeschreibung	PMID
Sf9	Function assay		Binding affinity to human recombinant full length N-terminal His-tagged PI3Kgamma expressed in Sf9 insect cells by equilibrium fluorescence titration analysis, Kd = 0.00029 μM.	27660692
RAW264.7	Function assay	30 mins	Inhibition of PI3Kgamma in C5a-stimulated mouse RAW264.7 cells assessed as reduction in AKT phosphorylation at S473 incubated for 30 mins followed by stimulation with C5a for 3 mins by ELISA, IC50 = 0.0012 μM.	27660692
Sf9	Function assay	15 mins	Inhibition of human recombinant full length N-terminal His-tagged PI3Kgamma expressed in Sf9 insect cells using diC8PIP2 as substrate incubated for 15 mins followed by substrate addition measured after 2 hr by ADP-Glo luminescence assay, IC50 = 0.016 μM.	27660692
Sf9	Function assay		Binding affinity to human recombinant full length N-terminal His6-tagged PI3K p110alpha/p85alpha coexpressed in baculovirus infected Sf9 insect cells by equilibrium fluorescence titration analysis, Kd = 0.017 μM.	27660692
Sf9	Function assay		Binding affinity to human recombinant full length N-terminal GST-tagged PI3K p110delta/p85alpha coexpressed in baculovirus infected Sf9 insect cells by equilibrium fluorescence titration analysis, Kd = 0.023 μM.	27660692
Sf9	Function assay		Binding affinity to human recombinant full length N-terminal His6-tagged PI3K p110beta/p85alpha coexpressed in baculovirus infected Sf9 insect cells by equilibrium fluorescence titration analysis, Kd = 0.082 μM.	27660692
Raji	Function assay	30 mins	Inhibition of PI3Kdelta in IgM-stimulated human Raji cells assessed as reduction in AKT phosphorylation at S473 incubated for 30 mins followed by stimulation with IgM for 30 mins by ELISA, IC50 = 0.18 μM.	27660692
786-O	Function assay	30 mins	Inhibition of PI3Kbeta in human 786-O cells assessed as reduction in AKT phosphorylation at S473 after 30 mins by ELISA, IC50 = 0.24 μM.	27660692
SKOV-3	Function assay	30 mins	Inhibition of PI3Kalpha in human SKOV-3 cells assessed as reduction in AKT phosphorylation at S473 after 30 mins by ELISA, IC50 = 0.25 μM.	27660692
Sf9	Function assay	15 mins	Inhibition of human recombinant full length N-terminal His6-tagged PI3K p110alpha/p85alpha coexpressed in baculovirus infected Sf9 insect cells using diC8PIP2 as substrate incubated for 15 mins followed by substrate addition measured after 2 hr by ADP-Glo, IC50 = 3.2 μM.	27660692
Sf9	Function assay	15 mins	Inhibition of human recombinant full length N-terminal His6-tagged PI3K p110beta/p85alpha coexpressed in baculovirus infected Sf9 insect cells using diC8PIP2 as substrate incubated for 15 mins followed by substrate addition measured after 2 hr by ADP-Glo , IC50 = 3.5 μM.	27660692
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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht	528.56	Formel	C₃₀H₂₄N₈O₂	Lagerung (Ab dem Eingangsdatum)	3 Jahre-20°CPulver
CAS-Nr.	1693758-51-8	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	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

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 100 mg/mL (189.19 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : ˂1 mg/mL

Ethanol : ˂1 mg/mL

DMSO : 100 mg/mL (189.19 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Ethanol : 8 mg/mL

Water : Insoluble

DMSO : 100 mg/mL (189.19 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL (189.19 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewichtsrechner

In vivo Charge:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Von Selleck Labs validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, kontaktieren Sie unser Verkaufsteam für kundenspezifische Tests.	5.000mg/ml (9.46mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

Dosierung: mg/kg Durchschnittsgewicht der Tiere: g Dosiervolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH₂O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus (Mechanism of Action)

Targets/IC₅₀/Ki	PI3Kγ (Cell-free assay) 16 nM
In vitro	Eganelisib (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, this compound demonstrates excellent PI3K-γ potency (IC50 = 1.2 nM) and selectivity against other Class I PI3K isoforms (>146-fold). Furthermore, it dose dependently inhibits PI3K-γ-dependent bone marrow-derived macrophage (BMDM) migration in vitro. It 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).
In vivo	Eganelisib (IPI-549) has excellent oral bioavailability, low clearance, and distributes into tissues with a mean volume of distribution of 1.2 L/kg in vivo (mice, rats, dog, and monkeys). It has a favorable pharmacokinetic profile to allow potent and selective inhibition of PI3K-γ in vivo. This compound can significantly reduce neutrophil migration in a dose-dependent manner in mouse model when administered orally at all of the tested doses. In addition, it has been shown to inhibit tumor growth in murine syngeneic models through alteration of immune cells in the tumor microenvironment.
Literatur	[1] https://pubmed.ncbi.nlm.nih.gov/27660692/

Anwendungen (Applications)

Methoden	Biomarker	Bilder	PMID
Western blot	p-AKT / AKT / p-p65 / p65		27642729

Klinische Studieninformationen (Clinical Trial Information)

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer	Rekrutierung	Erkrankungen	Sponsor/Kooperationspartner	Startdatum	Phasen
NCT03980041	Completed	Bladder Cancer\|Urothelial Carcinoma\|Solid Tumor\|Advanced Cancer	Infinity Pharmaceuticals Inc.\|Bristol-Myers Squibb	September 25 2019	Phase 2
NCT02637531	Unknown status	Advanced Solid Tumors (Part A/B/C/D)\|Non-small Cell Lung Cancer (Part E)\|Melanoma (Part E)\|Squamous Cell Cancer of the Head and Neck (Part E)\|Triple Negative Breast Cancer (Part F)\|Adrenocortical Carcinoma (Part G)\|Mesothelioma (Part G)\|High-circulating Myeloid-derived Suppressor Cells (Part H)	Infinity Pharmaceuticals Inc.	December 2015	Phase 1

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Eganelisib (IPI-549) PI3Kγ-Inhibitor

Molekulargewicht: 528.56

Qualitätskontrolle (Quality Control)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Löslichkeit (Solubility)

Molaritätsrechner

In-vivo-Formulierungsrechner (Klare Lösung)

Wirkmechanismus (Mechanism of Action)

Anwendungen (Applications)

Klinische Studieninformationen (Clinical Trial Information)

Eganelisib (IPI-549) PI3Kγ-Inhibitor

Molekulargewicht: 528.56

Qualitätskontrolle (Quality Control)

Zellkultur, Behandlung & Arbeitskonzentration (Cell Culture, Treatment & Working Concentration)

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Löslichkeit (Solubility)

Molaritätsrechner

In-vivo-Formulierungsrechner (Klare Lösung)

Wirkmechanismus (Mechanism of Action)

Anwendungen (Applications)

Klinische Studieninformationen (Clinical Trial Information)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)