Linperlisib (YY-20394) is a potent, selective and orally active PI3Kδ inhibitor (IC50=4.6 nM), inhibitr PI3Kδ expressing human tumor cells growth both in vitro and in vivo.
Linperlisib (YY-20394) is less activity against PI3Kγ giving a kinase inhibition profile that is more PI3Kδ-selective by nearly 2 orders of magnitude
Linperlisib (YY-20394) significantly inhibited primary tumor growth in immune-competent mice with 4T1 and CT26 tumors, as well as 4T1 lung metastasis with dose dependency.
The anti-tumor efficacy of YY-20394 was largely mediated by T cells.
Linperlisib (YY-20394) synergistically enhanced the anti-tumor efficacy of anti-PD-L1 antibody in CT26 model and achieved long-term immune memory which is specific for CT26 tumors, but not for unrelated A20 tumors.
Linperlisib (YY-20394) significantly inhibited T cell differentiation into Treg both in mouse splenocyte and in human primary CD4+ T cells, and was especially potent inhibiting their IL-10 secretion in vitro.
Linperlisib (YY-20394) displayed significant anti-tumor efficacy in other syngeneic mouse tumor models tested including mouse colorectal cancer models MC-38 model in C57BL/c mice and CT26 model in BALB/c mice.