8XR5
Crystal structure of PD-L1 complexed with small molecule inhibitor X18
This is a non-PDB format compatible entry.
Summary for 8XR5
| Entry DOI | 10.2210/pdb8xr5/pdb |
| Descriptor | Programmed cell death 1 ligand 1, (2~{R})-2-[[2-(2,1,3-benzoxadiazol-5-ylmethoxy)-5-chloranyl-4-[[2-fluoranyl-3-[3-[3-(4-oxidanylpiperidin-1-yl)propoxy]phenyl]phenyl]methoxy]phenyl]methylamino]-3-oxidanyl-propanoic acid (3 entities in total) |
| Functional Keywords | programmed death-ligand 1, inhibitor, immunosuppressant, immunosuppressant-inhibitor complex, immunosuppressant/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 29608.17 |
| Authors | |
| Primary citation | Liu, L.,Zhang, H.,Hou, J.,Zhang, Y.,Wang, L.,Wang, S.,Yao, Z.,Xie, T.,Wen, X.,Xu, Q.,Dai, L.,Feng, Z.,Zhang, P.,Wu, Y.,Sun, H.,Liu, J.,Yuan, H. Discovery of Novel PD-L1 Small-Molecular Inhibitors with Potent In Vivo Anti-tumor Immune Activity. J.Med.Chem., 67:4977-4997, 2024 Cited by PubMed Abstract: Programmed death-ligand 1 (PD-L1) has surfaced as a promising therapeutic target for various cancers due to its pivotal role in facilitating tumor immune evasion. Herein, we report a series of novel small-molecule PD-L1 inhibitors exhibiting remarkable inhibitory activity against the PD-1/PD-L1 interaction (: IC = 1.3 nM) and reinstating the suppressive effect of PD-L1 on T cells (: EC = 152.8 nM). Crystallographic studies revealed the binding mode of and PD-L1. Through a rational prodrug design approach, we have successfully optimized the oral pharmacokinetic properties of , effectively addressing the poor oral pharmacokinetic profile of PD-L1 small-molecule inhibitors. Notably, demonstrated significant antitumor efficacy in murine models of MC38 and CT26 colon cancer through the upregulation of tumor infiltration and cytotoxicity of CD8 T cells partially. These findings offer promising prospects for the advancement of PD-L1 inhibitors as innovative agents in cancer immunotherapy. PubMed: 38465588DOI: 10.1021/acs.jmedchem.4c00102 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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