艾代拉里斯作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetIdelalisibCat. No.: HY-13026CAS No.: 870281-82-6分式: CHFNO分量: 415.42作靶點(diǎn): PI3K; Autophagy作通路: PI3K/Akt/mTOR; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 59.7 mg/mL (143.71 mM)* means soluble, but saturation unknown.SolventMass1 mg 5

2、 mg 10 mgConcentration制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照

3、In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.02 mM); Clear solution此案可獲得 2.5 mg/mL (6.02 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L

4、25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.02 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (6.02 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900

5、L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.02 mM); Clear solution此案可獲得 2.5 mg/mL (6.02 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Idelalisib (CAL-101; GS-1101)種服有效的選擇性 p110 抑制劑，IC50 為

6、 2.5 nM， p110 和其他 PI3K classI 酶的選擇性 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)體外研究 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.體內(nèi)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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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