CZC24832

카탈로그 번호S7018 배치:S701801

인쇄

기술 자료

화학식

C15H17FN6O2S
분자량 364.4 CAS 번호 1159824-67-5
용해도 (25°C)* 시험관 내(In vitro) DMSO 5 mg/mL (13.72 mM)
Water Insoluble
Ethanol Insoluble
생체 내(In Vivo) (개별적으로 순서대로 용매를 제품에 첨가하십시오.)
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.
* <1 mg/ml은 약간 용해되거나 불용해됨을 의미합니다.
* Selleck은 모든 화합물의 용해도를 자체적으로 테스트하며, 실제 용해도는 게시된 값과 약간 다를 수 있습니다. 이는 정상적인 현상이며, 약간의 배치 간 변동으로 인해 발생합니다.
* 실온 배송 (안정성 테스트 결과 이 제품은 냉각 조치 없이 배송될 수 있음을 보여줍니다.)

원액 준비

생물학적 활성

설명 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.
표적
PI3Kγ
(Cell-free assay)		 PI3Kβ
(Cell-free assay)
27 nM 1.1 μM
시험관 내(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 this compound 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 this compound 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, this compound inhibits TH17 cell differentiation.
생체 내(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 of this compound per kg body weight twice per day shows a substantial decrease of bone and cartilage destruction as well as of overall clinical parameters.

프로토콜 (참조)

동물 연구:[1]
  • 동물 모델

    therapeutic mouse CIA model

  • 용량

    3 mg/kg, 10 mg/kg

  • 투여

    Orally

참조

  • https://pubmed.ncbi.nlm.nih.gov/22544264/

고객 제품 검증

<p>(c) MM primary cells were treated with idelalisib (1 μm), CZC24832 (1 μm) and duvelisib (1 μm) for 72 h and then assessed for apoptosis by PI/Annexin V staining (n=4).</p>

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

For protein analysis, polymorphonuclear neutrophils (PMN) were activated with indicated stimuli (anti-TREM-1 antibody, matched control mAb, LPS) for 30 min after preincubated with idelalisib. Proteins were extracted with an urea-based lysis buffer, SDS PAGE was performed and proteins were blotted by a semi-dry process. Protein activation was analyzed by staining of phosphorylated and non-phosphorylated proteins. ß-actin served as loading control.

데이터 출처 [ , , Sci Rep, 2018, 8(1):5558 ]

Effect of PI3Kγ inhibitor on Akt phosphorylation. JVM3 cells were pre-incubated with the indicated concentrations of CZC4832 (in μM) and then stimulated with SDF1α for 10 min. Akt Ser473 phosphorylation and total Akt levels were assessed by Western blot.

데이터 출처 [ , , Leukemia, 2018, 32(9):1958-1969 ]

Selleck's CZC24832 인용됨 15 출판물

ATP-competitive inhibitors of PI3K enzymes demonstrate an isoform selective dual action by controlling membrane binding [ Biochem J, 2024, 481(23):1787-1802] PubMed: 39485310
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

반품 정책
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배송 및 보관
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