ArticleBiophysical journal2018
Dynamic Structural Differences between Human and Mouse STING Lead to Differing Sensitivity to DMXAA.
Article in Biophysical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- Nucleic acid sensing pathways in kidney disease development.Nature reviews. Nephrology · 2026Review
- Advancing Small-Molecule Immunotherapy Through Polymeric Micelle Delivery.Pharmaceutics · 2026Review
- Immune remodeling via mitochondria-dependent STING activation enhances cabozantinib response in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Advances and Strategies in Enhancing mRNA Cancer Vaccines.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Emerging cGAS-STING Agonist-Based Nanotherapeutics: Mechanistic Insights and Applications in Cancer Combination Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The STING Signaling: A Novel Target for Central Nervous System Diseases.Cellular and molecular neurobiology · 2025Review
- STING Agonist VB-85247 Induces Durable Antitumor Immune Responses by Intravesical Administration in a Non-Muscle-Invasive Bladder Cancer.Cancer research · 2025Article
- The STING signaling pathways and bacterial infection.Apoptosis : an international journal on programmed cell death · 2025Review
- Disulfiram/copper triggers cGAS-STING innate immunity pathway via ROS-induced DNA damage that potentiates antitumor response to PD-1 checkpoint blockade.International journal of biological sciences · 2025Article
- Emerging IO checkpoints in gastrointestinal oncology.Frontiers in immunology · 2025Review
- cGAS-STING pathway in systemic lupus erythematosus: biological implications and therapeutic opportunities.Immunologic research · 2024Review
- Activation of STING in pancreatic cancer-associated fibroblasts exerts an antitumor effect by enhancing tumor immunity.Scientific reports · 2024Article
- Plasmacytoid dendritic cells at the forefront of anti-cancer immunity: rewiring strategies for tumor microenvironment remodeling.Journal of experimental & clinical cancer research : CR · 2024Review
- The cGAS/STING Pathway-A New Potential Biotherapeutic Target for Gastric Cancer?Journal of personalized medicine · 2024Review
- Intratumoral delivery of the chitin-derived C100 adjuvant promotes robust STING, IFNAR, and CD8Cell reports. Medicine · 2024Article
- Harnessing innate immune pathways for therapeutic advancement in cancer.Signal transduction and targeted therapy · 2024Review
- Microglial STING activation alleviates nerve injury-induced neuropathic pain in male but not female mice.Brain, behavior, and immunity · 2024Article
- Understanding and therapeutically exploiting cGAS/STING signaling in glioblastoma.The Journal of clinical investigation · 2024Review
- Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors.Frontiers in immunology · 2024Review
- Small molecule innate immune modulators in cancer therapy.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stimulator-of-interferon-genes (STING) protein is involved in innate immunity. It has recently been shown that modulation of STING can lead to an aggressive antitumor response. DMXAA is an antitumor agent that had shown great promise in murine models but failed in human clinical trials. The molecular target of DMXAA was subsequently shown to be murine STING (mSTING); however, human STING (hSTING) is insensitive to DMXAA. Molecular dynamics simulations were employed to investigate the differences between hSTING and mSTING that could influence DMXAA binding. An initial set of simulations was performed to investigate a single lid region mutation G230I in hSTING (corresponding residue in mSTING is an Ile), which rendered the protein sensitive to DMXAA. The simulations found that an Ile side chain was enough to form a steric barrier that prevents exit of DMXAA, whereas in WT hSTING, the Gly residue that lacks a side chain formed a porous lid region that allowed DMXAA to exit. A second set of molecular dynamics simulations compared the tendency of STING to be in an open-inactive conformation or a closed-active conformation. The results show that hSTING prefers to be in an open-inactive conformation even with cGAMP, the native ligand, bound. On the other hand, mSTING prefers a closed-active conformation even without a ligand bound. These results highlight the challenges in translating a mouse active STING compound into a human active compound, while also providing avenues to pursue for designing a small-molecule drug targeting human STING.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.