Leniolisib

SKU: orb1226465

Description

A novel potent and selective PI3Kδ inhibitor with biochemical IC50 of 11 nM; displays >20-fold, 40-fold, and 200-fold selectivity over PI3Kα, PI3Kβ, and PI3Kγ, respectively; shows 30-fold cellular selectivity over PI3Kα; inhibits a large spectrum of immune cell functions, as demonstrated in B and T cells, neutrophils, monocytes, basophils, plasmocytoid dendritic cells, and mast cells in vitro; potently inhibits antigen-specific antibody production and reduces disease symptoms in a rat collagen-induced arthritis model.Other Indication Phase 2 Clinical(In Vitro):Expression of APDS mutant p110δ in cell lines and patient-derived lymphocytes lead to increased pathway activity, measured as phosphorylation of AKT or S6, which is suppressed by leniolisib in a concentration dependent way.(In Vivo):Oral leniolisib lead to a dose-dependent reduction in PI3K/AKT pathway activity and resolve the immune dysregulation with normalization of circulating transitional and na ve B cells and reduction in PD-1+CD4+ and senescent CD57+CD8+ T cells. After 12 weeks of treatment, all patients show amelioration of lymphoproliferation with lymph node sizes and spleen volumes reduced by 39% (mean, range 26-57%) and 40% (mean, range: 13-65%), respectively.

Key Properties

• CAS Number: 1354690-24-6
• MW: 450.4574
• Purity: >98% (HPLC)
• Formula: C₂₁H₂₅F₃N₆O₂
• SMILES: CCC(=O)N1CCC(C1)NC2=NC=NC3=C2CN(CC3)C4=CC(=C(N=C4)OC)C(F)(F)F
• Target: PI3K
• Solubility: DMSO: ≥150 mg/mL

Bioactivity

• In Vivo:
  Oral leniolisib lead to a dose-dependent reduction in PI3K/AKT pathway activity and resolve the immune dysregulation with normalization of circulating transitional and na ve B cells and reduction in PD-1+CD4+ and senescent CD57+CD8+ T cells. After 12 weeks of treatment, all patients show amelioration of lymphoproliferation with lymph node sizes and spleen volumes reduced by 39% (mean, range 26-57%) and 40% (mean, range: 13-65%), respectively.
• In Vitro:
  Expression of APDS mutant p110δ in cell lines and patient-derived lymphocytes lead to increased pathway activity, measured as phosphorylation of AKT or S6, which is suppressed by leniolisib in a concentration dependent way.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CDZ-173 | CDZ173

Quick Database Links

Gene Symbol

PI3K