ArticleOncoimmunology2020
Small-molecule PD-L1 inhibitor BMS1166 abrogates the function of PD-L1 by blocking its ER export.
Article in Oncoimmunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- MS1-96 induces HIP1R-dependent PD-L1 degradation and promotes antitumor immunity in colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Small molecules targeting the PD-1/PD-L1 axis for cancer immunotherapy.Theranostics · 2026Review
- Targeting PD-1 in Squamous Cell Carcinoma: Flavonoid-based Therapeutics Unveiled throughCurrent computer-aided drug design · 2026Article
- Structure-based virtual screening identifies potent CD28 inhibitors that suppress T cell co-stimulation in cellular and mucosal models.European journal of medicinal chemistry · 2025Article
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Targeted Delivery of BMS-1166 for Enhanced Breast Cancer Immunotherapy.International journal of nanomedicine · 2025Article
- Endoplasmic Reticulum Stress Induces ROS Production and Activates NLRP3 Inflammasome Via the PERK-CHOP Signaling Pathway in Dry Eye Disease.Investigative ophthalmology & visual science · 2024Article
- Zosuquidar Promotes Antitumor Immunity by Inducing Autophagic Degradation of PD-L1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Glycosylation in the tumor immune response: the bitter side of sweetness.Acta biochimica et biophysica Sinica · 2024Review
- Molecular glues for protein-protein interactions: Progressing toward a new dream.Cell chemical biology · 2024Review
- Posttranslational regulatory mechanism of PD-L1 in cancers and associated opportunities for novel small-molecule therapeutics.Acta biochimica et biophysica Sinica · 2024Review
- Beyond inhibition against the PD-1/PD-L1 pathway: development of PD-L1 inhibitors targeting internalization and degradation of PD-L1.RSC medicinal chemistry · 2024Review
- Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD-L1 in Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Innovative virtual screening of PD-L1 inhibitors: the synergy of molecular similarity, neural networks and GNINA docking.Future medicinal chemistry · 2024Article
- Targeting PD-1/PD-L-1 immune checkpoint inhibition for cancer immunotherapy: success and challenges.Frontiers in immunology · 2024Review
- Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies.Biotechnology advances · 2023Review
- Design, Synthesis, and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile as PD-L1 Antagonist and Its Comparison to Available Small Molecular PD-L1 Inhibitors.Journal of medicinal chemistry · 2023Article
- PD-L1 Exon 3 Is a Hidden Switch of Its Expression and Function in Oral Cancer Cells.International journal of molecular sciences · 2023Article
- Raloxifene, a SERM targets PD-L1: an in-silico study.American journal of translational research · 2023Article
- The Glycosylation of Immune Checkpoints and Their Applications in Oncology.Pharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic monoclonal antibodies against the PD-L1/PD-1 (programmed death ligand-1/programmed cell death protein-1) axis have achieved great successes in cancer treatments, but the development of small-molecule immunomodulators of the pathway has lagged far behind. We established a cellular coculture assay with two stable transfectant cell lines, a PD-L1-expressing tumor cell line PC9/PD-L1 and a PD-1-expressing T cell line Jurkat/PD-1. Western blotting analyses were used to monitor the PD-L1/PD-1 interaction and signaling. We analyzed PD-L1 glycosylation by lectin binding assay and glycosidase digestion, and examined subcellular localization of PD-L1 by immunocytochemical staining. Luciferase assay and real-time PCR were used to evaluate T cell activation in the coculture experiments. We found that coculturing of the PC9/PD-L1 cells with the Jurkat/PD-1 cells induced a lysosomal degradation of PD-1. A small-molecule PD-L1 inhibitor BMS1166 developed by Bristol-Myers Squibb inhibited the coculture-induced PD-1 degradation through a unique mechanism. BMS1166 specifically affected PD-L1 glycosylation and prevented transporting of the under-glycosylated form of PD-L1 from endoplasmic reticulum (ER) to Golgi, leading to accumulation of PD-L1 in ER. In doing so, BMS1166 blocked PD-L1/PD-1 signaling. Coculturing PD-L1-expressing cells with PD-1-expressing cells induced degradation of PD-1, which could be used as a readout to identify inhibitors of PD-L1/PD-1 signaling. The small-molecule PD-L1 inhibitor BMS1166 abolished the glycosylation and maturation of PD-L1 by blocking its exporting from ER to Golgi. Our study discovered a new strategy to identify inhibitors of the PD-L1/PD-1 signaling pathway and to develop new drugs for the treatment of cancer.
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