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Synonyms | GS-1101 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C22H18FN7O |
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分子量 | 415.42 | CAS No. | 870281-82-6 | |
Solubility (25°C)* | 体外 | DMSO | 83 mg/mL warmed with 50ºC water bath (199.79 mM) | |
Ethanol | 83 mg/mL (199.79 mM) | |||
Water | 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. |
製品説明 | Idelalisib (CAL-101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy. |
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in vitro | CAL-101 is not sensitive to other PI3K class I subunits including p110α, p110β, and p110γ. CAL-101 specifically blocks FcϵR1 p110δ-mediated CD63 expression with an EC50 of 8 nM in primary basophil. CAL-101 exhibits greater activity in B-cell acute lymphoblastic leukemia (B-ALL) and chronic lymphocytic leukemia (CLL) cells compared with acute myeloid leukemia (AML) and myeloproliferative neoplasm (MPN) cells. CAL-101 produces the reduction in pAktS473, pAktT308, and the downstream target S6 in SU-DHL-5, KARPAS-422 and CCRF-SB cells with EC50 of 0.1 to 1.0 μM. [1] CAL-101 induces selective cytotoxicity in CLL cells independent of IgVH mutational status or interphase cytogenetics, primarily through a caspase-dependent mechanism. CAL-101 induces cytotoxicity preferentially to CLL cells compared with normal B cells, without producing cytotoxicity in other hematopoietic cells, compared to LY294002. CAL-101 lacks direct cytotoxic potential to T cells and nature killer (NK) cells. CAL-101 can inhibit production of inflammatory cytokines, such as IL-6, IL-10, TNF-α, and IFN-γ, and activation-induced cytokines, such as CD40L. CAL-101 also antagonizes CD40L-mediated CLL cell survival. [2] CAL-101 induces an accumulation of cells in G1 and a decrease in the S-phase population in L1236 and L591 cells, which indicates CAL-101 as a novel strategy for the treatment of hodgkin lymphoma (HL). [3] |
キナーゼアッセイ | PI3K assay | |
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PI3K assay is preformed on whole-cell lysates from CLL or normal B cells. A PI3K ELISA assay is performed. Briefly, whole-cell extracts are added to a mixture of PI(4,5)P2 substrate and reaction buffer containing adenosine triphosphate (ATP) and allowed to incubate at room temperature. The reaction is stopped by adding PI(3,4,5)P3 detector mixed with EDTA (ethylenediaminetetraacetic acid) and allowed to incubate at room temperature for 1 hour. After this time, the mixture is transferred from each well to a PI3K ELISA plate and allowed to incubate 1 hour. Plates are washed and then incubated with secondary detector for 30 minutes. Plates are washed again, and 3,3′,5,5′-tetramethylbenzidine solution is added for 5 minutes at which time H2SO4 is added to stop all reactions. Plates are read at 450 nm on a Labsystems 96-well plate reader. | ||
細胞アッセイ | 細胞株 | CLL B cells or healthy volunteer T cells or NK cells |
濃度 | 0.01-100 μM | |
反応時間 | 48 hours | |
実験の流れ | MTT assays are performed to determine cytotoxicity. 1 × 105 cells are incubated with CAL-101. MTT reagent is then added, and plates are incubated for an additional 20 hours before washing with protamine sulfate in phosphate-buffered saline. DMSO is added, and absorbance is measured by spectrophotometry at 540 nm in a Labsystems plate reader. Cell viability is also measured at various time points with the use of annexin/PI flow cytometry. Data are analyzed. At least 104 cells are counted for each sample. Results are expressed as the percentage of total positive cells over untreated control. Experiments examining caspase-dependent apoptosis included the addition of 100 μM Z-VAD. Experiments examining survival signals include the addition of 1 μg/mL CD40L, 800 U/mL IL-4, 50 ng/mL BAFF, 20 ng/mL TNF-α, or coculturing on fibronectin or stromal (HS-5 cell line) coated plates. Stromal coculture is done by plating a 75-cm2 flask (80%-100% confluent) per 6-well plate 24 hours before the addition of CLL cells. |
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動物実験 | 動物モデル | C57BL/6 mice |
投薬量 | 40 mg/kg | |
投与方法 |
Data from [Data independently produced by Cell Death Differ, 2014, 21(10), 1535-45]
Data from [Data independently produced by Acta Pharmacol Sin, 2013, 34(9),1201-7]
, , Dr. Zhang of Tianjin Medical University
The highly selective and oral phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib induces apoptosis in mesothelioma cells and increases immune effector cell composition [ Transl Oncol, 2024, 43:101857] | PubMed: 38412661 |
Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma [ Cancer Cell, 2023, 41(6):1103-1117.e12] | PubMed: 37207655 |
PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma [ Nat Cancer, 2023, 4(10):1508-1525] | PubMed: 37723306 |
Alcam-a and Pdgfr-α are essential for the development of sclerotome-derived stromal cells that support hematopoiesis [ Nat Commun, 2023, 14(1):1171] | PubMed: 36859431 |
Dasatinib overcomes glucocorticoid resistance in B-cell acute lymphoblastic leukemia [ Nat Commun, 2023, 14(1):2935] | PubMed: 37217509 |
Integrated single-cell (phospho-)protein and RNA detection uncovers phenotypic characteristics and active signal transduction of human antibody secreting cells [ Mol Cell Proteomics, 2023, S1535-9476(23)00001-4] | PubMed: 36623694 |
Intrinsic cancer cell phosphoinositide 3-kinase δ regulates fibrosis and vascular development in cholangiocarcinoma [ Liver Int, 2023, 10.1111/liv.15751] | PubMed: 37804055 |
Activation of glucagon-like peptide-1 receptor in microglia exerts protective effects against sepsis-induced encephalopathy via attenuating endoplasmic reticulum stress-associated inflammation and apoptosis in a mouse model of sepsis [ Exp Neurol, 2023, 363:114348] | PubMed: 36813224 |
A combination of BR101801 and venetoclax enhances antitumor effect in DLBCL cells via c-Myc/Bcl-2/Mcl-1 triple targeting [ Am J Cancer Res, 2023, 13(2):452-463] | PubMed: 36895970 |
Senolytic Flavonoids Enhance Type-I and Type-II Cell Death in Human Radioresistant Colon Cancer Cells through AMPK/MAPK Pathway [ Cancers (Basel), 2023, 15(9)2660] | PubMed: 37174126 |
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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