艾代拉里斯作用机制 - Medchemexpress - MCE中国

1、Product Data SheetIdelalisibCat. No.: HY-13026CAS No.: 870281-82-6分式: CHFNO分量: 415.42作靶点: PI3K; Autophagy作通路: PI3K/Akt/mTOR; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 59.7 mg/mL (143.71 mM)* means soluble, but saturation unknown.SolventMass1 mg 5

2、 mg 10 mgConcentration制备储备液1 mM 2.4072 mL 12.0360 mL 24.0720 mL5 mM 0.4814 mL 2.4072 mL 4.8144 mL10 mM 0.2407 mL 1.2036 mL 2.4072 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照

3、In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.02 mM); Clear solution此案可获得 2.5 mg/mL (6.02 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L

4、25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.02 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (6.02 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900

5、L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.02 mM); Clear solution此案可获得 2.5 mg/mL (6.02 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Idelalisib (CAL-101; GS-1101)种服有效的选择性 p110 抑制剂，IC50 为

6、 2.5 nM， p110 和其他 PI3K classI 酶的选择性 40 到 300 倍。IC & Target p110 p110 p110 p1102.5 nM (IC50) 89 nM (IC50) 565 nM (IC50) 820 nM (IC50)hVps34 DNA-PK978 nM (IC50) 6729 nM (IC50)体外研究 Idelalisib (CAL-101; GS-1101) is a highly selective and potent p110 inhibitor (EC50=8 nM). Greater selectivity (400- to400

7、0-fold) is seen against related kinases C2, hVPS34, DNA-PK, and mTOR, whereas no activity is observed against apanel of 402 diverse kinases at 10 M. CAL-101 reduces PDGF-induced pAkt by only 25% at 10 M. Idelalisib (CAL-101) inhibits LPA-induced pAkt with an EC50 of 1.9 M. Idelalisib (CAL-101) block

8、s FcRI p110-mediated CD63expression with an EC50 of 8 nM, whereas formyl-methionyl-leucyl-phenylalanine activation of p110 is inhibited withan EC50 of 3 M. Thus, in cell-based assays, CAL-101 has 240- to 2500-fold selectivity for p110 over the other class IPI3K isoforms1. CAL-101Idelalisib (CAL-101)

9、-induced apoptosis of chronic lymphocytic leukemia (CLL) cells issignificant compare with vehicle treatment alone (P0.001). Idelalisib (CAL-101) induces selective cytotoxicity in CLLcells independent of IgVH mutational status or interphase cytogenetics2.体内研究 A significant reduction is observed in th

10、e CD11b+Ly6G+ neutrophils from brain homogenates of bothp110D910A/D910A mice and Idelalisib (CAL-101) (40 mg/kg, i.v.) post-treated mice3.PROTOCOLCell Assay 2 MTT assays are performed to determine cytotoxicity. Briefly, 1105 cells (CLL B cells or healthy volunteer T cells or NKcells) are incubated f

11、or 48 hours with different concentrations of Idelalisib (CAL-101) (0.1 M, 1 M, 5 M, 10 M), 25M LY294002, or vehicle control. MTT reagent is then added. DMSO is added, and absorbance is measured byspectrophotometry at 540 nm in a Labsystems plate reader. Cell viability is also measured at various tim

12、e points withthe use of annexin/PI flow cytometry. Data are analyzed with Expo-ADC32 software package. At least 10,000 cells arecounted for each sample. Results are expressed as the percentage of total positive cells over untreated control.Experiments examining caspase-dependent apoptosis included t

13、he addition of 100 M Z-VAD. Experimentsexamining survival signals include the addition of 1 g/mL CD40L, 800 U/mL IL-4, 50 ng/mL BAFF, 20 ng/mL TNF-,or coculturing on fibronectin or stromal (HS-5 cell line) coated plates. Stromal coculture is done by plating a 75-cm2flask (80%-100% confluent) per 6-w

14、ell plate 24 hours before the addition of CLL cells2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice3Page 2 of 3 www.MedChemEAdministration 3 For Idelalisib (CAL-101) treatment, wild-type C57BL/6 mice are administered either 40 mg/kg Idelali

15、sib (CAL-101) orvehicle DMSO, by 25 L infusion into the femoral vein, 15 min before I/R (pre-treatment), or 3 and 6 h after initiationof reperfusion (post-treatment). Controls and animals treated with Idelalisib (CAL-101) underwent cerebral blood flow(CBF) measurements using a laser Doppler perfusio

16、n monitor. The CBF measurements obtained immediately beforeand after MCAO and again at 3 h after reperfusion showed an 90-95% reduction in the blood flow to the MCAOinfarct region, which does not differ between groups.MCE has not independently confirmed the accuracy of these methods. They are for re

17、ference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Leukemia. 2015 Jan;29(1):169-76. Clin Cancer Res. 2018 Mar 1;24(5):1103-1113. Cell Syst. 2020 Jan 22;10(1):66-81.e11. Cell Syst. 2018 Dec.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Lann

18、utti BJ, et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signalingand cellular viability. Blood, 2011, 117(2), 591-594.2. Herman SE, et al. Phosphatidylinositol 3-kinase- inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizingintrinsic and ex