CZC24832

製品コードS7018 バッチS701801

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

C15H17FN6O2S
分子量 364.4 CAS No. 1159824-67-5
Solubility (25°C)* 体外 DMSO 5 mg/mL warmed with 50ºC water bath (13.72 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 CZC24832 is the first selective PI3Kγ inhibitor with IC50 of 27 nM, with 10-fold selectivity over PI3Kβ and >100-fold selectivity over PI3Kα and PI3Kδ.
in vitro CZC24832 has excellent selectivity to PI3Kγ. Out of the 154 identified lipid and protein kinases and the 922 other proteins, only two off targets (PI3Kβ and PIP4K2C) are detected within a 100-fold selectivity window. Despite the high sequence conservation of the human and rodent class I PI3K isoforms, the potency of CZC24832 for PI3Kγ and PI3Kβ is consistently lower by a factor of 2 to 4 in mice and rats compared to humans, but selectivity windows are largely retained. In the BT system, treatment with CZC24832 results in profound inhibition of IL-17A (IC50 =1.5 μM) as well as of B-cell activation markers such as IL-6 and IgG. In addition, strong inhibition of IL17A production is observed in T-cell systems such as human umbilical vein endothelial cells grown in the presence of TH2 blasts, indicating a general role for PI3Kγ kinase activity in the control of TH17 function. Thus, CZC24832 inhibits TH17 cell differentiation. [1]
in vivo In an IL-8–dependent air pouch model, CZC24832 shows a dose dependent reduction of granulocyte recruitment consistent with the degree of inhibition observed in PI3Kγ-null mice. In a therapeutic collagen induced arthritis (CIA) model, mice treated orally with 10 mg CZC24832 per kg body weight twice per day shows a substantial decrease of bone and cartilage destruction as well as of overall clinical parameters. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Compound screening
Competition binding assays using the LK matrix are performed essentially as described above but adapted to a 384-well format. 0.25 mg of cell lysate and 2.5 μL of beads are used per well. Compounds from the screening library including reference compounds as standards are added at 40 μM final concentration from 50× DMSO stocks. Each plate contains 15 positive and 17 negative controls. After 2 hrs binding at 4 °C, the non-bound fraction is removed by washing the beads with lysis buffer. Proteins retained on the beads are eluted in SDS sample buffer and spotted on nitrocellulose membranes (400 nL/spot) using an automated pin tool liquid transfer. After drying, the membranes are rehydrated in 20% ethanol, and processed for detection with specific antibodies as indicated, followed by incubation with a labeled secondary antibody for visualization. Spot intensities are quantified using a scanner and percentage inhibition is calculated using positive and negative controls as 100% and 0% inhibition, respectively.
動物実験 動物モデル therapeutic mouse CIA model
投薬量 3 mg/kg, 10 mg/kg
投与方法 Orally

カスタマーフィードバック

, , Blood Cancer J, 2017, 7(3):e539

Data from [Data independently produced by , , Sci Rep, 2018, 8(1):5558]

Data from [Data independently produced by , , Leukemia, 2018, 32(9):1958-1969]

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：

Roles of PI3Kγ and PI3Kδ in mantle cell lymphoma proliferation and migration contributing to efficacy of the PI3Kγ/δ inhibitor duvelisib [ Sci Rep, 2023, 13(1):3793] PubMed: 36882482
Combined Treatment with PI3K Inhibitors BYL-719 and CAL-101 Is a Promising Antiproliferative Strategy in Human Rhabdomyosarcoma Cells [ Molecules, 2022, 27(9)2742] PubMed: 35566091
Time Series Transcriptomic Analysis by RNA Sequencing Reveals a Key Role of PI3K in Sepsis-Induced Myocardial Injury in Mice [ Front Physiol, 2022, 13:903164] PubMed: 35721566
Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury [ Kidney Blood Press Res, 2022, 47(10):616-630] PubMed: 36130530
HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G1/S cycle [ Autophagy, 2021, 1-19] PubMed: 33866937
Electrotaxis of Glioblastoma and Medulloblastoma Spheroidal Aggregates. [ Sci Rep, 2019, 9(1):5309] PubMed: 30926929
PI3Kβ is selectively required for growth factor-stimulated macropinocytosis [ J Cell Sci, 2019, 132(16)jcs231639] PubMed: 31409694
Distinct roles for phosphoinositide 3-kinases γ and δ in malignant B cell migration [Ali AY Leukemia, 2018, 32(9):1958-1969] PubMed: 29479062
p110α Inhibition Overcomes Stromal Cell-Mediated Ibrutinib Resistance in Mantle Cell Lymphoma [Guan J Mol Cancer Ther, 2018, 17(5):1090-1100] PubMed: 29483220
Idelalisib impairs TREM-1 mediated neutrophil inflammatory responses [Alflen A Sci Rep, 2018, 8(1):5558] PubMed: 29615799

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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