leniolisib

Ligand id: 9424

Name: leniolisib

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 83.48
Molecular weight 450.2
XLogP 2.47
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Being evaluated in clinical trial in patients with genetically activated PI3Kδ (i.e. patients with APDS/PASLI; see Phase 2/3 trial NCT02435173). Positive results from NCT02435173 are reported by Rao et al. (2017) [4], showing that leniolisib was well tolerated and improved laboratory and clinical parameters in APDS patients.
Mechanism Of Action and Pharmacodynamic Effects
Gain-of-function mutations in PI3Kδ causes hyperactivation of mTOR signaling, which in turn skews the differentiation of CD8+ T cells to short-lived effector cells and severely impairs development of functional memory T cells and B cells. Inhibition of aberrant PI3Kδ activity is predicted to restore T cell differentiation and T and B cell function.