9INU

Novel PD-L1/VISTA dual inhibitor as potential immunotherapy agents

This is a non-PDB format compatible entry.

Summary for 9INU

• Entry DOI: 10.2210/pdb9inu/pdb
• Descriptor: Programmed cell death 1 ligand 1, (2~{S})-2-[[6-methoxy-2-[(2-methyl-3-phenyl-phenyl)amino]pyrimidin-4-yl]methylamino]-3-oxidanyl-propanoic acid (3 entities in total)
• Functional Keywords: immune checkpoint, small molecular inhibitor, dimer, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 29765.97

Authors

Cheng, Y.,Xiao, Y.B. (deposition date: 2024-07-08, release date: 2025-03-12)

Primary citation

Sun, C.,Cheng, Y.,Dong, J.,Hu, L.,Zhang, Y.,Shen, H.,Zhang, G.,Jiang, B.,Adam Youssouf, S.,Min, W.,Shen, Y.,Wang, L.,Deng, H.,Xiao, Y.,Yang, P.
Novel PD-L1/VISTA Dual Inhibitor as Potential Immunotherapy Agents.
J.Med.Chem., 68:156-173, 2025

PubMed Abstract: Inhibiting the activity of immune checkpoint proteins to reignite the antitumor activity of immune cells has emerged as a pivotal strategy. PD-L1 and VISTA, as critical proteins governing immune regulation, are concurrently upregulated under conditions such as hypoxia. Through a rational drug design process, , a dual-target inhibitor for PD-L1 and VISTA is identified. This inhibitor blocks the signaling pathways of both PD-L1 and VISTA at the protein and cellular levels, thereby reactivating the antitumor function of T cells. displays encouraging attributes in terms of druggability and safety assessments. Notably, demonstrates superior antitumor efficacy compared to single-target inhibitors at equivalent doses in in vivo experiments. More crucially, significantly enhances the infiltration of immune cells. This study not only validates the effectiveness of a dual-target inhibitor strategy against PD-L1 and VISTA, but also identifies as a promising candidate molecule with significant therapeutic potential.

PubMed: 39731560
DOI: 10.1021/acs.jmedchem.4c01640

Experimental method

X-RAY DIFFRACTION (2.7 Å)