IPI-3063 - PI3K 抑制劑 - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIPI-3063Cat. No.: HY-111510CAS No.: 1425043-73-7分式: CHNO分量: 455.51作靶點: PI3K作通路: PI3K/Akt/mTOR儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 83.33 mg/mL (182.94 mM)* means soluble, but satu

2、ration unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.1953 mL 10.9767 mL 21.9534 mL5 mM 0.4391 mL 2.1953 mL 4.3907 mL10 mM 0.2195 mL 1.0977 mL 2.1953 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 IPI-3063種有效的選擇性 PI3K p110 抑制劑，IC50 為 2.51.2 nM。IC50 & Target p110 p

3、110 p110 p1102.5 nM (IC50) 1170 nM (IC50) 1508 nM (IC50) 2187 nM (IC50)體外研究IPI-3063 inhibits p110, p110, and p110 with IC50s of 1171533 nM, 1508624 nM, and 21871529 nM,1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemErespectively. IPI-3063 potently reduces mouse B cell proliferation, survival, and p

4、lasmablast differentiationwhile increasing antibody class switching to IgG1. IPI-3063 is a p110 selective compound with an IC50=0.1nM in p110-specific cell-based assays and cellular IC50 values for the other class I PI3K isoforms are atleast 1,000-fold higher (IC50=19011318 nM for p110, IC50=102.835

5、.7 nM for p110, IC50=418.8117.2nM for p110). IPI-3063 is very potent in reducing p-AKT (significant effect at 1nM). IPI-3063 also reduces p-ERK1/2 with a significant effect at 10nM. IPI-3063 is very potent, achieving a significant decrease in B cellsurvival when present at 10nM 1.PROTOCOLKinase Assa

6、y 1 Human recombinant PI3K-, PI3K-, PI3K-, and PI3K- are used. Phosphatidylinositol 4,5 bis phosphate(diC8-PtdIns(4,5)P2) is used. PI3K-, , and are heterodimers consisting of full length p110, p110, orp110 catalytic subunit and the p85 regulatory subunit. PI3K- is a monomer of the p110 catalytic sub

7、unit.Samples of kinase (10nM-, , and ; 20nM-) are incubated with IPI-3063 for 30min at room temperaturein reaction buffer (15mM HEPES pH 7.4, 20mM NaCl, 1mM EGTA, 0.02% Tween 20, 10mM MgCl2, 0.2mg/mL bovine-globulins) followed by addition of ATP/diC8-PtdIns(4,5)P2 mixture to give finalconcentrations

8、 of 3mM ATP and 500M diC8-PtdIns(4,5)P2. Reactions are incubated at room temperaturefor 2h, with PI3K activity is assessed. Plates are read on plate reader in luminescence mode 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Peripheral bl

9、ood mononuclear cells (PBMCs) are first purified from blood by density gradient centrifugation.Human B cells are then purified from PBMCs by negative selection. B-cell purity is increased from 4% to70% as measured by FACS analysis using anti-CD19 PE conjugated antibody. Purified B cells are seededat

10、 a final concentration of 0.1106cells/mL and cultured with 2g/mL human CD40L+5g/mL anti-humanIgM/IgG+100g/mL hIL-2+100g/mL hIL-21. All B cells are cultured in RPMI 1640 supplemented with 10%(vol/vol) heat-inactivated FCS, 5mM Hepes, 2mM L-glutamine, 100U/mL Penicillin, 100g/mLStreptomycin, 50M 2-mer

11、captoethanol. Purified human B cells are pretreated with IPI-3063 (0.1, 1, 10, and100nM) for 30min, then stimulated with human CD40L+anti-human IgM/IgG+human IL-2+human IL-21 for120h 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Chiu H, et al. The Selective Phosphoinoside-3-Kinase p110 Inhibitor IPI-3063 Potently Suppresses B Cell Survival, Proliferation, andDifferentiation. Front Immunol. 2017 Jun 30;8:747.McePdfHeightCaution: Product