Eganelisib (IPI-549)

製品コードS8330 バッチS833002

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C30H24N8O2
分子量 528.56 CAS No. 1693758-51-8
Solubility (25°C)* 体外 DMSO 100 mg/mL (189.19 mM)
Water Insoluble
Ethanol Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 SKOV-3 cells
濃度 --
反応時間 30 min
実験の流れ

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.
動物実験 動物モデル CD-1 mice, Sprague-Dawley rats, beagle dogs and cynomolgus monkeys.
投薬量 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)
投与方法 p.o.; i.v.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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