9LJ3

Crystal structure of P25

This is a non-PDB format compatible entry.

Summary for 9LJ3

• Entry DOI: 10.2210/pdb9lj3/pdb
• Descriptor: Programmed cell death 1 ligand 1, 3-[[4-chloranyl-2-[(2-hydroxyethylamino)methyl]-5-[[2-methyl-3-[3-[2-[2-[(3~{R})-3-oxidanylpyrrolidin-1-yl]ethoxy]ethoxy]phenyl]phenyl]methoxy]phenoxy]methyl]benzenecarbonitrile (3 entities in total)
• Functional Keywords: pd-l1, p25, complex, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 87398.24

Authors

Yang, P.,Chen, M.R.,Xiao, Y.B. (deposition date: 2025-01-14, release date: 2025-06-25, Last modification date: 2025-07-09)

Primary citation

Yang, Z.,Yang, P.,Xu, J.,Yang, X.,Zhou, J.,He, H.,Li, L.,Ren, Y.,Chen, M.,Xiao, Y.,Chen, J.
Discovery and Crystallography Study of Novel Resorcinol Dibenzyl Ether-Based PD-1/PD-L1 Inhibitors with Improved Drug-like and Pharmacokinetic Properties for Cancer Treatment.
J.Med.Chem., 68:12593-12614, 2025

PubMed Abstract: Current studies on PD-1/PD-L1 small-molecule inhibitors mainly focus on modifying the linker region between the biphenyl ring and amino acid side chains, or transforming the biphenyl ring into a benzodioxane structure. Herein, we designed and synthesized a series of compounds by introducing a tail at the terminal phenyl ring as small-molecule PD-1/PD-L1 inhibitors. Among them, compound exhibited the most potent PD-L1 inhibitory activity (IC = 24.4 nM). The X-ray crystal structure further confirmed the high binding affinity of to PD-L1 dimer. In the HepG2/Jurkat T cell coculture model, promoted HepG2 cell apoptosis dose-dependently. In addition, showed excellent antitumor efficacy (TGI = 92.1%) in a Hepa1-6 mouse tumor model and increased CD8 cells in tumor microenvironment. Importantly, possessed favorable pharmacokinetic properties with an oral bioavailability of 15.9%. Collectively, compound represents a promising PD-1/PD-L1 inhibitor worthy of further investigation as a potential anticancer agent.

PubMed: 40518797
DOI: 10.1021/acs.jmedchem.5c00344

Experimental method

X-RAY DIFFRACTION (3.15 Å)