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Purity: ≥98%
Seletalisib (formerly known as UCB-5857) is a novel, potent, ATP-competitive, and selective, small-molecule inhibitor of PI3Kδ with an IC50 value of 12 nM. It exhibits significant (between 24- and 303-fold) preferential binding to PI3K in comparison to the other class I PI3K isoforms.and its effectiveness was examined using biochemical tests, cellular tests of innate and adaptive immunity, and an in vivo rat model of inflammation. When the B-cell receptor is activated in a B-cell line, seletalisib has the ability to prevent protein kinase B (AKT) phosphorylation. Seletalisib also prevented human neutrophils from releasing superoxide when they were stimulated by N-formyl peptide, but not when they were stimulated by phorbol myristate acetate, suggesting that it has PI3Kδ-specific activity. Peripheral blood mononuclear cells (PBMCs) and other cell types that were exposed to seletalisib showed no signs of cytotoxicity. Results from cellular assays of adaptive immunity showed that seletalisib inhibits human T-cell production of a number of cytokines from activated T-cells. Furthermore, seletalisib reduced B-cell proliferation and cytokine production. Seletalisib reduced the expression of CD69 in human whole blood assays after B-cell activation and anti-IgE-mediated basophil degranulation. In an in vivo rat model of anti-CD3-antibody-induced interleukin 2 release, seletalisib showed dose-dependent inhibition. Collectively, these data define seletalisib as a selective PI3K inhibitor and potential therapeutic candidate for the treatment of autoimmune diseases and B-cell malignancies caused by dysregulated proinflammatory cytokine secretion.
| Targets |
PI3Kδ (IC50 = 12 nM); GSK-3α (IC50 = 1.5 nM)
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| Enzyme Assay |
Seletalisib is dissolved 1 mM solution in DMSO and tested in a concentration response (seletalisib), to explore the effects of PI3Kδ-specific inhibition compared with complete inhibition of class I PI3K signaling. Additionally, the effects of seletalisib at 1000, 100, 10, and 1 nM are examined in the BioMap BT cell system. Based on how the compounds affect cellular readout levels like cytokines, growth factors, adhesion molecules, and proliferation endpoints, an activity profile is created[1].
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| Cell Assay |
Serially diluted seletalisib and goat anti-human F(ab)2 IgM in serum-free RPMI 1640 were added to Ramos cells plated in serum-free RPMI 1640. The plate was incubated for 10 minutes, placed on ice, and the cells were centrifuged to pellet them. The MSD assay was used to identify cellularly phosphorylated AKT.
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| Animal Protocol |
Rats: Rats receive seletalisib (0.1-10 mg/kg in 500 μL volume) or vehicle via oral gavage 30 min before receiving a 200 μL dose volume of anti-CD3 antibody intravenously. For oral and intravenous administration, the vehicle is methylcellulose or saline, respectively. Levels of IL-2 and seletalisib are measured[1].
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| References |
| Molecular Formula |
C23H14CLF3N6O
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| Molecular Weight |
482.85
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| Exact Mass |
482.08697
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| Elemental Analysis |
C, 57.21; H, 2.92; Cl, 7.34; F, 11.80; N, 17.41; O, 3.31
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| CAS # |
1362850-20-1
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
C1=CC2=CC(=C(N=C2C(=C1)Cl)C3=C[N+](=CC=C3)[O-])[C@H](C(F)(F)F)NC4=NC=NC5=C4N=CC=C5
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| InChi Key |
LNLJHGXOFYUARS-OAQYLSRUSA-N
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| InChi Code |
InChI=1S/C23H14ClF3N6O/c24-16-6-1-4-13-10-15(18(31-19(13)16)14-5-3-9-33(34)11-14)21(23(25,26)27)32-22-20-17(29-12-30-22)7-2-8-28-20/h1-12,21H,(H,29,30,32)/t21-/m1/s1
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| Chemical Name |
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0710 mL | 10.3552 mL | 20.7104 mL | |
| 5 mM | 0.4142 mL | 2.0710 mL | 4.1421 mL | |
| 10 mM | 0.2071 mL | 1.0355 mL | 2.0710 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Seletalisib is a selective, ATP-competitive PI3Kδinhibitor.
Seletalisib is a potent inhibitor of IL-2 release in a rat model of inflammation (primary pharmacology model).J Pharmacol Exp Ther.2017 Jun;361(3):429-440 |
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Seletalisib shows potent and selective cellular inhibition of PI3Kδsignaling.
Seletalisib shows potent activity in human whole blood assays.J Pharmacol Exp Ther.2017 Jun;361(3):429-440 |
Seletalisib shows anti-inflammatory activity in cellular assays of adaptive immunity.J Pharmacol Exp Ther.2017 Jun;361(3):429-440 |
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