Evidence map›Paper›PMID 33354501›Full record

ReviewActa pharmaceutica Sinica. B2020

Small molecules targeting the innate immune cGAS‒STING‒TBK1 signaling pathway.

Chunyong Ding, Zilan Song, Ancheng Shen, Tingting Chen, Ao Zhang

Open access · diamondAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Acta pharmaceutica Sinica. B, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed
11.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

168 citing papers in PubMed, 285 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
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  6. Article
  7. Review
  8. Article
  9. [Mechanisms of cGAS-STING-mediated chronic inflammation and targeted interventions in brain aging].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026
    Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. cGAS-STING signaling in pollution-induced toxicity: mechanism and relieving medication.Apoptosis : an international journal on programmed cell death · 2026
    Review
  18. Article
  19. Article
  20. Article

108 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Chunyong DingResearch Laboratory of Medicinal Chemical Biology & Frontiers on Drug Discovery (RLMCBFDD), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Zilan SongCAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Ancheng ShenCAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Tingting ChenCAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
Ao ZhangResearch Laboratory of Medicinal Chemical Biology & Frontiers on Drug Discovery (RLMCBFDD), School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Shanghai Institute of Materia Medica · CNChinese Academy of Sciences · CNShanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors (ICIs) have been successfully developed to treat various cancers by motivating the adaptive anti-tumor immunity. Particularly, the checkpoint blockade approach has achieved great clinic success as evidenced by several U.S. Food and Drug Administration (FDA)-approved anti-programmed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 antibodies. However, the majority of cancers have low clinical response rates to these ICIs due to poor tumor immunogenicity. Indeed, the cyclic guanosine monophosphate-adenosine monophosphate synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS‒STING‒TBK1) axis is now appreciated as the major signaling pathway in innate immune response across different species. Aberrant signaling of this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection and cancers. In this perspective, we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS‒STING‒TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory therapy. Meanwhile, highlights on the clinical candidates, limitations and challenges, as well as future directions in this field are also discussed. Further, small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well.

Indexed as

ABZI, amidobenzimidazoleACMA, 9-amino-6-chloro-2-methoxyacridineAMP, adenosine monophosphateAnti-tumorATP, adenosine triphosphateBNBC, 6-bromo-N-(naphthalen-1-yl)benzo[d][1,3]dioxole-5-carboxamidecAIMP, cyclic adenosine-inosine monophosphateCBD, cyclic dinucleotide-binding domainCDA, cyclic diadenosine monophosphate (c-di-AMP)CDG, cyclic diguanosine monophosphate (c-di-GMP)CDN, cyclic dinucleotidecGAMP, cyclic guanosine monophosphate-adenosine monophosphatecGAScGAS, cyclic guanosine monophosphate-adenosine monophosphate synthaseCMA, 10-carboxymethyl-9-acridanoneCTD, C-terminal domainCTLA-4, cytotoxic T lymphocyte associated protein 4CTT, C-terminal tailCXCL, chemokine (C-X-C motif) ligandDC50, concentration for 50% degradationDCs, dendritic cellsDMXAA, 5,6-dimethylxanthenone-4-acetic aciddsDNA, double-stranded DNADSDP, dispiro diketopiperzineEM, cryo-electron microscopyENPP1, ecto-nucleotide pyrophosphatase/phosphodiesteraseER, endoplasmic reticulumFAA, flavone-8-acetic acidFDA, U.S. Food and Drug AdministrationFP, fluorescence polarizationGMP, guanosine monophosphateGTP, guanosine triphosphateHCQ, hydrochloroquineHTS, high throughput screeningICI, immune checkpoint inhibitorIKK, IκB kinaseImmunotherapyIO, immune-oncologyIRF3, interferon regulatory factor 3ISG, interferon stimulated geneITC, isothermal titration calorimetryi.t., intratumoralKD, kinase domainLBD, ligand-binding domainMDCK, Madin–Darby canine kidneyMG, MangostinMI, maximum inductionMinEC5×, minimum effective concentration for inducing 5-fold luciferase activityMLK, mixed lineage kinaseNF-κB, nuclear factor-κBNtase, nucleotidyl transferasePBMCs, peripheral-blood mononuclear cellsPD-1, programmed death receptor 1PDE, phosphodiesterasesPDK1, 3-phosphoinositide-dependent protein kinase 1PD-L1, programmed death ligand 1PPi, pyrophosphoric acidPROTACs, proteolysis targeting chimerasPRRs, pattern recognition receptorsQC, quinacrineSAR, structure–activity relationshipSDD, scaffold and dimerization domainSmall molecule modulatorsSTAT, signal transducer and activator of transcriptionSTINGSTING, stimulator of interferon genesTBK1TBK1, TANK-binding kinase 1THIQCs, tetrahydroisoquinolone acetic acidsTNFRSF, tumor necrosis factor receptor superfamilyULD, ubiquitin-like domainVHL, von Hippel–Lindau

Identifiers

PMID33354501
PMCPMC7745059
OpenAlexW3011178559

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.