7NLD

Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass inhibitor

Summary for 7NLD

• Entry DOI: 10.2210/pdb7nld/pdb
• Descriptor: Programmed cell death 1 ligand 1, N-(2-((2'-chloro-3'-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-methoxy-[1,1'-biphenyl]-4-yl)(methyl)amino)ethyl)methanesulfonamide (3 entities in total)
• Functional Keywords: pd-l1, cancer, inhibitor, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 89581.58

Authors

Sala, D.,Magiera-Mularz, K.,Muszak, D.,Surmiak, E.,Grudnik, P.,Holak, T.A. (deposition date: 2021-02-22, release date: 2021-08-11, Last modification date: 2024-01-31)

Primary citation

Muszak, D.,Surmiak, E.,Plewka, J.,Magiera-Mularz, K.,Kocik-Krol, J.,Musielak, B.,Sala, D.,Kitel, R.,Stec, M.,Weglarczyk, K.,Siedlar, M.,Domling, A.,Skalniak, L.,Holak, T.A.
Terphenyl-Based Small-Molecule Inhibitors of Programmed Cell Death-1/Programmed Death-Ligand 1 Protein-Protein Interaction.
J.Med.Chem., 64:11614-11636, 2021

PubMed Abstract: We describe a new class of potent PD-L1/PD-1 inhibitors based on a terphenyl scaffold that is derived from the rigidified biphenyl-inspired structure. Using docking, we designed and then experimentally demonstrated the effectiveness of the terphenyl-based scaffolds in inhibiting PD-1/PD-L1 complex formation using various biophysical and biochemical techniques. We also present a high-resolution structure of the complex of PD-L1 with one of our most potent inhibitors to identify key PD-L1/inhibitor interactions at the molecular level. In addition, we show the efficacy of our most potent inhibitors in activating the antitumor response using primary human immune cells from healthy donors.

PubMed: 34313116
DOI: 10.1021/acs.jmedchem.1c00957

Experimental method

X-RAY DIFFRACTION (2.3 Å)