Discovery of potent and selective PI3Kδ inhibitors bearing amino acid fragments

•A series of novel compounds containing amino acid fragments were designed as potent and selective PI3Kδ inhibitors.•Compound A10 showed potent PI3Kδ inhibitory activity with an IC50 value of 0.9 nM. A10 demonstrated selective anti-proliferative activity against SU-DHL-6 cell line with an IC50 value of IC50 = 0.20 μM.•A10 significantly reduced the phosphorylation of Akt, which was approximately comparable to that of idelalisib.•The docking study showed that A10 tightly bound to PI3Kδ protein with a planar-shaped conformation.