IPI-3063
Modify Date: 2024-01-09 17:57:56
IPI-3063 structure
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Common Name | IPI-3063 | ||
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| CAS Number | 1425043-73-7 | Molecular Weight | 455.512 | |
| Density | 1.4±0.1 g/cm3 | Boiling Point | 817.8±65.0 °C at 760 mmHg | |
| Molecular Formula | C25H25N7O2 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | 448.4±34.3 °C | |
Use of IPI-3063IPI-3063 is a potent and selective PI3K p110δ inhibitor with an IC50 of 2.5 ± 1.2 nM. |
| Name | IPI-3063 |
|---|---|
| Synonym | More Synonyms |
| Description | IPI-3063 is a potent and selective PI3K p110δ inhibitor with an IC50 of 2.5 ± 1.2 nM. |
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| Related Catalog | |
| Target |
p110δ:2.5 nM (IC50) p110α:1170 nM (IC50) p110β:1508 nM (IC50) p110γ:2187 nM (IC50) |
| In Vitro | IPI-3063 inhibits p110α, p110β, and p110γ with IC50s of 1171±533 nM, 1508±624 nM, and 2187±1529 nM, respectively. IPI-3063 potently reduces mouse B cell proliferation, survival, and plasmablast differentiation while increasing antibody class switching to IgG1. IPI-3063 is a p110δ selective compound with an IC50=0.1 nM in p110δ-specific cell-based assays and cellular IC50 values for the other class I PI3K isoforms are at least 1,000-fold higher (IC50=1901±1318 nM for p110α, IC50=102.8±35.7 nM for p110β, IC50=418.8±117.2 nM for p110γ). IPI-3063 is very potent in reducing p-AKT (significant effect at 1 nM). IPI-3063 also reduces p-ERK1/2 with a significant effect at 10 nM. IPI-3063 is very potent, achieving a significant decrease in B cell survival when present at 10 nM[1]. |
| Kinase Assay | Human recombinant PI3K-α, PI3K-β, PI3K-δ, and PI3K-γ are used. Phosphatidylinositol 4,5 bis phosphate (diC8-PtdIns(4,5)P2) is used. PI3K-α, β, and δ are heterodimers consisting of full length p110α, p110β, or p110δ catalytic subunit and the p85α regulatory subunit. PI3K-γ is a monomer of the p110γ catalytic subunit. Samples of kinase (10 nM-α, β, and δ; 20 nM-γ) are incubated with IPI-3063 for 30 min at room temperature in reaction buffer (15 mM HEPES pH 7.4, 20 mM NaCl, 1 mM EGTA, 0.02% Tween 20, 10 mM MgCl2, 0.2 mg/mL bovine-γ-globulins) followed by addition of ATP/diC8-PtdIns(4,5)P2 mixture to give final concentrations of 3 mM ATP and 500 µM diC8-PtdIns(4,5)P2. Reactions are incubated at room temperature for 2 h, with PI3K activity is assessed. Plates are read on plate reader in luminescence mode[1]. |
| Cell Assay | Peripheral blood 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% to >70% as measured by FACS analysis using anti-CD19 PE conjugated antibody. Purified B cells are seeded at a final concentration of 0.1×106 cells/mL and cultured with 2 µg/mL human CD40L+5 µg/mL anti-human IgM/IgG+100 µg/mL hIL-2+100 µg/mL hIL-21. All B cells are cultured in RPMI 1640 supplemented with 10% (vol/vol) heat-inactivated FCS, 5 mM Hepes, 2 mM L-glutamine, 100 U/mL Penicillin, 100 µg/mL Streptomycin, 50 µM 2-mercaptoethanol. Purified human B cells are pretreated with IPI-3063 (0.1, 1, 10, and 100 nM) for 30 min, then stimulated with human CD40L+anti-human IgM/IgG+human IL-2+human IL-21 for 120 h[1]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 817.8±65.0 °C at 760 mmHg |
| Molecular Formula | C25H25N7O2 |
| Molecular Weight | 455.512 |
| Flash Point | 448.4±34.3 °C |
| Exact Mass | 455.206970 |
| LogP | 3.10 |
| Vapour Pressure | 0.0±2.9 mmHg at 25°C |
| Index of Refraction | 1.688 |
| Storage condition | -20℃ |
| 4-Amino-6-({(1S)-1-[2-isopropyl-8-(1-methyl-6-oxo-1,6-dihydro-3-pyridinyl)-1-oxo-1,2-dihydro-3-isoquinolinyl]ethyl}amino)-5-pyrimidinecarbonitrile |
| 5-Pyrimidinecarbonitrile, 4-amino-6-[[(1S)-1-[8-(1,6-dihydro-1-methyl-6-oxo-3-pyridinyl)-1,2-dihydro-2-(1-methylethyl)-1-oxo-3-isoquinolinyl]ethyl]amino]- |