7NLD

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

7NLD の概要

• エントリーDOI: 10.2210/pdb7nld/pdb
• 分子名称: 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)
• 機能のキーワード: pd-l1, cancer, inhibitor, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 89581.58

構造登録者

Sala, D.,Magiera-Mularz, K.,Muszak, D.,Surmiak, E.,Grudnik, P.,Holak, T.A. (登録日: 2021-02-22, 公開日: 2021-08-11, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.3 Å)