Discovery of bromobenzyl phenyl ether derivative YPD-29B: a novel pre-clinical compound targeting the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) interaction.

Targeting the PD-1/PD-L1 immune checkpoint pathway with small molecules has exhibited great promise. Herein, to develop the inhibitors with good activity, pharmacokinetic properties and druggability, a novel series of halogens substituted derivatives at the 2-position of the biphenyl group were synthesized, screened, and their inhibitory activity against the PD-1/PD-L1 protein-protein interaction (PPI) was evaluated through a HTRF assay. Among them, YPD-29B exhibited potent activity with IC value of less than 1 pM.

Targeting HNRNPA2B1 inhibits enterovirus 71 replication in SK-N-SH cells.

Objective: To investigate the effect of heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) on the replication of enterovirus 71 (EV-71) in SK-N-SH cells.

Methods: The mRNA and protein expression of HNRNPA2B1 in SK-N-SH cells were detected by real-time quantitative PCR (qRT-PCR) and western blotting (WB), respectively. WB was used to detect HNRNPA2B1 protein expression in the nucleus and cytosol.

Design, synthesis, and structure-activity relationship of PD-1/PD-L1 inhibitors with a benzo[d]isoxazole scaffold.

Blocking the programmed cell death protein 1 (PD-1) and programmed death-ligand (PD-L1) interaction has emerged as one of the most promising treatments for cancer immunotherapy. A novel series of compounds bearing a benzo[d]isoxazole scaffold was developed as PD-1/PD-L1 inhibitors, among them, compound P20 exhibited the most potent inhibitory activity, with an IC value of 26.8 nM.

MAPK/c-Jun signaling pathway contributes to the upregulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL induced by Epstein-Barr virus-encoded in gastric carcinoma cells.

, encoded by Epstein-Barr virus (EBV), has been hypothesized to function as an oncogene, which was expressed in gastric carcinoma cells. Additionally, it has been reported that the anti-apoptotic function is closely associated with the expression of the B-cell lymphoma-2 (Bcl-2) protein. In addition, the signaling pathway has been reported to be involved in numerous diseases, including the mitogen-activated protein kinase (MAPK) cascade.