STING1

Summary

STING1 (stimulator of interferon response cGAMP interactor 1, HGNC:27962) is a protein-coding gene on chromosome 5q31.2, encoding Stimulator of interferon genes protein (Q86WV6). Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta).

This gene encodes a five transmembrane protein that functions as a major regulator of the innate immune response to viral and bacterial infections. The encoded protein is a pattern recognition receptor that detects cytosolic nucleic acids and transmits signals that activate type I interferon responses. The encoded protein has also been shown to play a role in apoptotic signaling by associating with type II major histocompatibility complex. Mutations in this gene are the cause of infantile-onset STING-associated vasculopathy. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 340061 — RefSeq curated summary.

At a glance

• Gene–disease (curated): STING-associated vasculopathy with onset in infancy (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 341 total — 5 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_198282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27962
Approved symbol	STING1
Name	stimulator of interferon response cGAMP interactor 1
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38577, NET23, ERIS, MPYS, STING, MITA
Ensembl gene	ENSG00000184584
Ensembl biotype	protein_coding
OMIM	612374
Entrez	340061

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 12 retained_intron, 9 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000330794, ENST00000502362, ENST00000502825, ENST00000503287, ENST00000503838, ENST00000507297, ENST00000509573, ENST00000511850, ENST00000511886, ENST00000512606, ENST00000514119, ENST00000514348, ENST00000514542, ENST00000515507, ENST00000650883, ENST00000651565, ENST00000651699, ENST00000652110, ENST00000652271, ENST00000652293, ENST00000652543, ENST00000652640, ENST00000861780, ENST00000971036, ENST00000971037

RefSeq mRNA: 3 — MANE Select: NM_198282 NM_001301738, NM_001367258, NM_198282

CCDS: CCDS4215, CCDS93791, CCDS93792

Canonical transcript exons

ENST00000330794 — 8 exons

Exon	Start	End
ENSE00001519554	139482210	139482302
ENSE00002046380	139482550	139482758
ENSE00003634329	139481159	139481342
ENSE00003650276	139480790	139480898
ENSE00003663810	139481478	139481704
ENSE00003678195	139477329	139477515
ENSE00003790916	139478270	139478508
ENSE00003845754	139475533	139476454

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6895 / max 351.5253, expressed in 1562 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63763	13.2870	1435
63768	8.0405	1373
63762	3.2499	1059
63767	0.9692	541
63765	0.8856	578
63766	0.7738	445
63764	0.4834	307

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.98	gold quality
granulocyte	CL:0000094	97.95	gold quality
mucosa of stomach	UBERON:0001199	97.30	gold quality
fallopian tube	UBERON:0003889	97.06	gold quality
right coronary artery	UBERON:0001625	96.98	gold quality
upper lobe of left lung	UBERON:0008952	96.94	gold quality
descending thoracic aorta	UBERON:0002345	96.82	gold quality
left uterine tube	UBERON:0001303	96.65	gold quality
apex of heart	UBERON:0002098	96.58	gold quality
thoracic aorta	UBERON:0001515	96.54	gold quality
ascending aorta	UBERON:0001496	96.52	gold quality
spleen	UBERON:0002106	96.50	gold quality
leukocyte	CL:0000738	96.27	gold quality
left coronary artery	UBERON:0001626	96.18	gold quality
monocyte	CL:0000576	96.17	gold quality
endocervix	UBERON:0000458	96.08	gold quality
vermiform appendix	UBERON:0001154	96.08	gold quality
right atrium auricular region	UBERON:0006631	96.03	gold quality
tibial artery	UBERON:0007610	95.80	gold quality
popliteal artery	UBERON:0002250	95.78	gold quality
smooth muscle tissue	UBERON:0001135	95.72	gold quality
lung	UBERON:0002048	95.56	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.53	gold quality
right lung	UBERON:0002167	95.46	gold quality
adipose tissue	UBERON:0001013	95.27	gold quality
lymph node	UBERON:0000029	95.13	gold quality
omental fat pad	UBERON:0010414	95.00	gold quality
body of uterus	UBERON:0009853	94.83	gold quality
ectocervix	UBERON:0012249	94.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.89
E-MTAB-9801	yes	6.55
E-MTAB-5061	yes	6.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, MYC

miRNA regulators (miRDB)

31 targeting STING1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-6816-3P	95.05	66.08	459
HSA-MIR-5684	93.17	64.85	454

Literature-anchored findings (GeneRIF, showing 40)

• STING (TMEM173) is an endoplasmic reticulum adaptor protein that facilitates innate immune signaling (PMID:18724357)
• identification, following expression cloning, of a molecule (STING; stimulator of interferon genes) that appears essential for effective innate immune signalling processes (PMID:18724357)
• results suggest MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity. (PMID:18818105)
• E3 ubiquitin ligase RNF5 interacted with MITA in a viral-infection-dependent manner (PMID:19285439)
• dimerization of ERIS was critical for self-activation and subsequent downstream signaling (PMID:19433799)
• Cellular reactive oxygen species inhibit MPYS induction of IFNbeta (PMID:21170271)
• R71H-G230A-R293Q haplotype MPYS exhibits a > 90% loss in the ability to stimulate IFNbeta production (PMID:21248775)
• DDX41 is an additional DNA sensor that depends on STING to sense pathogenic DNA. (PMID:21892174)
• a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction (PMID:22312431)
• study now shows that in response to cytosolic double-stranded DNA, the C-terminal tail of STING provides a scaffold to assemble IRF3 and TBK1, which leads to TBK1-dependent phosphorylation of IRF3 (PMID:22394560)
• results suggest that STING functions as a scaffold protein to specify and promote the phosphorylation of IRF3 by TBK1. (PMID:22394562)
• results indicate that interaction between the pattern recognition receptor RIG-I and the adapter molecule STING, is a major contributor to elicit immunological responses involving the type 1 interferons in neurons following JEV infections (PMID:22470840)
• We elucidate the structural features of the cytosolic c-di-GMP binding domain (CBD) of STING and its complex with c-di-GMP (PMID:22705373)
• virus-cell fusion is sensed by the innate immune system and activates a STING-dependent signaling pathway that leads to the production of type I interferon and molecules encoded by interferon-stimulated genes (PMID:22706339)
• Guanines of c-di-GMP stack against the phenolic rings of a conserved tyrosinein STING, and mutations at the c-di-GMP binding surface reduce nucleotide binding and affect signaling (PMID:22728658)
• report here the crystal structures of the STING cytoplasmic domain and its complex with c-di-GMP, thus providing the structural basis for understanding STING function (PMID:22728659)
• In response to c-di-GMP binding, two surface loops, which serve as a gate and latch of the cleft formed by the dimeric STING(CTD), undergo rearrangements to interact with the ligand (PMID:22728660)
• TRIM32 protein modulates type I interferon induction and cellular antiviral response by targeting MITA/STING protein for K63-linked ubiquitination (PMID:22745133)
• we identified MITA as a novel host target of dengue virus protease (PMID:22761576)
• Hepatitis C virus NS4B suppresses RIG-I-mediated IFN-beta production signaling through a direct protein interaction with STING. (PMID:22911572)
• study describes the mechanism of inhibition of type I IFN production by Dengue virus in primary cells and identify the adaptor molecule STING as a target of the DENV NS2B3 protease complex (PMID:23055924)
• STING instigates cytoplasmic DNA-mediated cellular defense gene transcription and facilitates adoptive responses that are required for protection of the host. (PMID:23478444)
• Mechanistic studies indicated that NS4B disrupts the interactions between STING/MITA and TBK1, an additional mechanism for HCV evasion of host interferon responses. (PMID:23542348)
• study identified STING as a direct receptor for 6-dimethylxanthenone-4-acetic acid (DMXAA) leading to TANK-binding kinase 1 and IFN regulatory factor 3 signaling; the ability to sense DMXAA was restricted to murine STING; human STING failed to bind to or signal in response to DMXAA (PMID:23585680)
• Chlamydia induces STING-mediated IFN responses through the detection of c-di-AMP in the host cell cytosol and propose that c-di-AMP is the ligand predominantly responsible for inducing such a response in Chlamydia-infected cells. (PMID:23631912)
• The hSTING variants have evolved to distinguish conventional (3’-5’) cyclic dinucleotides from the noncanonical cyclic dinucleotide produced by mammalian cGAS. (PMID:23707065)
• cGAS produces a 2’-5’-linked cyclic dinucleotide second messenger that activates STING (PMID:23722158)
• Study shows that human hSTING(H232) adopts a “closed” conformation upon binding c[G(2’,5’)pA(3’,5’)p] and its linkage isomer c[G(2’,5’)pA(2’,5’)p], as does mouse mSting(R231) on binding c[G(2’,5’)pA(3’,5’)p], c[G(3’,5’)pA(3’,5’)p] (PMID:23910378)
• Data indicate that cyclic GMP-AMP synthase (cGAS) is important for the stimulator of interferon genes (STING)-dependent immune activation (PMID:24116191)
• After activation and trafficking, STING is phosphorylated by UNC-51-like kinase (ULK1). This occurs following ULK1 dissociation from its repressor AMPK and was found to be triggered by cGAS-generated cyclic dinucleotides. (PMID:24119841)
• This study provides a mechanistic explanation for abortive HTLV-1 infection of monocytes and reports a link between SAMHD1 restriction, HTLV-1 reverse transcription intermediate sensing by STING, and initiation of IRF3-Bax driven apoptosis. (PMID:24139400)
• Single nucleotide polymorphisms of human STING is associated with innate immune response to cyclic dinucleotides. (PMID:24204993)
• Data indicate that NF-kappaB leads to elevated expression of TNF-alpha sensitizing mediator of IRF3 activation (MITA) induced cell death. (PMID:24239807)
• An alternatively spliced isoform of MITA lacking exon 7, shares the N-terminal portion aa 1-253 with MITA but has a unique 30-aa sequence at the carboxyl terminal. MRP is as a dominant negative regulator of MITA-mediated induction of IFN production. (PMID:24391220)
• STING is stable in cancer-derived HEp-2 or HeLa cells infected with wild-type HSV-1 but is degraded in cells infected with mutants lacking the genes encoding functional infected cell protein 0 (ICP0), ICP4, or the US3 protein kinase. (PMID:24449861)
• This study demonstrates that E2 proteins of high risk human papillomavirus reduce STING and IFN-kappa transcription. (PMID:24614210)
• the molecular mechanisms of MITA-mediated signal transduction and regulation (PMID:24929887)
• The mechanism of double-stranded DNA sensing through the cGAS-STING pathway. (PMID:25007740)
• STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (PMID:25029335)
• antagonism of STING signalling during RNA virus infection. (PMID:25212897)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sting1	ENSDARG00000091058
mus_musculus	Sting1	ENSMUSG00000024349
rattus_norvegicus	Sting1	ENSRNOG00000042137
drosophila_melanogaster	Sting	FBGN0033453

Protein

Protein identifiers

Stimulator of interferon genes protein — Q86WV6 (reviewed: Q86WV6)

Alternative names: Endoplasmic reticulum interferon stimulator, Mediator of IRF3 activation, Transmembrane protein 173

All UniProt accessions (5): Q86WV6, A0A494C0T1, A0A494C0W5, A0A494C1N5, J3QTB1

UniProt curated annotations — full annotation on UniProt →

Function. Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, cyclic UMP-AMP (2’,3’-cUAMP), and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol. Upon binding to c-di-GMP, cUAMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state. Exhibits 2’,3’ phosphodiester linkage-specific ligand recognition: can bind both 2’-3’ linked cGAMP (2’-3’-cGAMP) and 3’-3’ linked cGAMP but is preferentially activated by 2’-3’ linked cGAMP. The preference for 2’-3’-cGAMP, compared to other linkage isomers is probably due to the ligand itself, whichs adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation. In addition to promote the production of type I interferons, plays a direct role in autophagy. Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome. Promotes autophagy by acting as a proton channel that directs proton efflux from the Golgi to facilitate MAP1LC3B/LC3B lipidation. The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation. Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Involved in intercellular immune signaling. Cross-activated by 2’,3’-cGAMP previously generated in virus-infected cells, triggers type I interferon signaling in macrophages and uninfected neighboring cells to propagate and amplify the antiviral immune response. (Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein. Such oncoproteins prevent the ability to sense cytosolic DNA.

Subunit / interactions. Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP); ‘Lys-63’-linked ubiquitination at Lys-150 is required for homodimerization. Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing. Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3. Interacts with RIGI, MAVS and SSR2. Interacts with RNF5 and TRIM56. Interacts with TBK1; when homodimer, leading to subsequent production of IFN-beta. Interacts with IFIT1 and IFIT2. Interacts with TRIM29; this interaction induces STING1 ubiquitination and subsequent degradation. Associates with the MHC-II complex. Interacts with STEEP1; interaction takes place upon cGAMP-activation and STING1 phosphorylation by MAP3K7/TAK1 and promotes STING1 translocation to COPII vesicles. Interacts with SEC24A, SEC24B, and SEC24C; promoting translocation to COPII vesicles. Interacts (when ubiquitinated) with SQSTM1; leading to relocalization to autophagosomes. Interacts with SURF4. Interacts with HNRNPA2B1. Interacts with ZDHHC1; ZDHHC1 constitutively interacts with STING1 and in presence of DNA viruses activates it by promoting its cGAMP-induced oligomerization and the recruitment of downstream signaling components. Interacts with ZDHHC11; in presence of DNA viruses promotes the recruitment of IRF3 to STING1. Interacts with TOMM70. Interacts with isoform IFI16-beta of IFI16. Interacts with TAB1; promoting recruitment of TAB1 to the endoplasmic reticulum membrane and subsequent activation of MAP3K7/TAK1. Interacts (via transmembrane domain) with TMEM203. Interacts with DDX41. Interacts with TMEM120A (via C-terminal domain); regulates the trafficking of STING1 from the ER to the ER-Golgi intermediate compartment to elicit antiviral effects. (Microbial infection) Interacts with human papillomavirus (HPV) protein E7. (Microbial infection) Interacts with adenovirus early E1A protein. (Microbial infection) Interacts with herpes simplex virus 1 protein ICP34.5; this interaction inhibits the intracellular DNA sensing pathway. (Microbial infection) Interacts with Chikungunya virus non-structural protein 1; this interaction results in inhibition of cGAS-STING signaling and increased levels of palmitoylated nsP1 and protein stabilization. (Microbial infection) Interacts with human cytomegalovirus proteins UL94, UL42 and UL138; these interactions result in the inhibition of cGAS-STING signaling. (Microbial infection) Interacts with varivella virus protein 39; this interaction results in the inhibition of cGAS-STING signaling.

Subcellular location. Endoplasmic reticulum membrane. Cytoplasm. Perinuclear region. Endoplasmic reticulum-Golgi intermediate compartment membrane. Golgi apparatus membrane. Cytoplasmic vesicle. Autophagosome membrane. Mitochondrion outer membrane. Cell membrane.

Tissue specificity. Ubiquitously expressed. Expressed in skin endothelial cells, alveolar type 2 pneumocytes, bronchial epithelium and alveolar macrophages.

Post-translational modifications. Phosphorylation by TBK1 leads to activation and production of IFN-beta. Following cyclic nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation from the endoplasmic reticulum, STING1 is phosphorylated by TBK1 at Ser-366 in the pLxIS motif. The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines. The phosphorylated pLxIS motif facilitates SENP2 recruitment during late phase of viral infection. Phosphorylated on tyrosine residues upon MHC-II aggregation. Dephosphorylation by PPP6C leads to inactivation and decreased production of IFN-beta. Phosphorylation at Ser-358 is also required to activate IRF3. Phosphorylation at Ser-355 by MAP3K7/TAK1 facilitates its interaction with STEEP1, promoting STING1 translocation to COPII vesicles. Ubiquitinated. Ubiquitinated via ‘Lys-63’-linked ubiquitin chains in response to double-stranded DNA treatment, leading to relocalization to autophagosomes and subsequent degradation; this process is dependent on SQSTM1. ‘Lys-63’-linked ubiquitination mediated by TRIM56 at Lys-150 promotes homodimerization and recruitment of the antiviral kinase TBK1 and subsequent production of IFN-beta. ‘Lys-48’-linked polyubiquitination at Lys-150 occurring after viral infection is mediated by RNF5 and leads to proteasomal degradation. ‘Lys-11’-linked polyubiquitination at Lys-150 by RNF26 leads to stabilize STING1: it protects STING1 from RNF5-mediated ‘Lys-48’-linked polyubiquitination. ‘Lys-33’-linked and ‘Lys-48’-linked deubiquitinated by USP20; leading to its stabilization and promotion of innate antiviral response. ‘Lys-48’-linked deubiquitinated by USP44; leading to its stabilization and promotion of innate antiviral response. Deubiquitinated by USP13; leading to inhibition of innate antiviral response. ‘Lys-63’-linked deubiquitinated by USP49; leading to inhibition of the subsequent recruitment of TBK1 to the signaling complex. ‘Lys-63’-linked ubiquitination mediated by RNF39 promotes the activation of the cGAS-STING pathway. MARCHF5-mediated ubiquitination prevents the oxidation-induced polymer formation. (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 on both ‘Lys-48’ and ‘Lys-63’-linked ubiquitin chains; leading to inhibition of cGAS-STING signaling. Sumoylated at Lys-338 by TRIM38 during the early phase of viral infection, promoting its stability by preventing its relocalization to autophagosomes and subsequent degradation. Desumoylated by SENP2 during the late phase of viral infection. Palmitoylation takes place in the Golgi apparatus and creates a platform for the recruitment of TBK1.

Disease relevance. STING-associated vasculopathy, infantile-onset (SAVI) [MIM:615934] An autoinflammatory disease characterized by early-onset systemic inflammation and cutaneous vasculopathy, resulting in severe skin lesions. Violaceous, scaling lesions of fingers, toes, nose, cheeks and ears progress to acral necrosis in most of the patients. Some patients have severe interstitial lung disease. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated upon binding to the hydrolysis-resistant 2'3’-cG(s)A(s)MP, an analog of cGAMP, in which phosphodiester linkages are replaced by phosphothioate linkages. Specifically inhibited by small-molecule H-151 (N-(4-ethylphenyl)-N’-1H-indol-3-yl-urea), which covalently binds Cys-91 and prevents palmitoylation and subsequent activation of STING1. In contrast to mouse protein, not activated by anticancer molecule 5,6-dimethylxanthenone 4-acetic acid (DMXAA). Inhibited by compound 18 ([(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]acetate), a competitive inhibitor with slow dissociation kinetics and good oral bioavailability. Homooligomerization and ability to promote the production of type I interferons is activated by C53, a small benzothiazinone-like compound that binds to the transmembrane regions. in the area of the putative pore. In contrast, compound C53, directly inhibits the proton channel activity and facilitate MAP1LC3B/LC3B lipidation and autophagosome formation.

Domain organisation. In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly. In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing. The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD. The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines. The N-terminal domain interacts with glycerophospholipids and phospholipids.

Miscellaneous. The cGAS-STING signaling pathway drives sterile inflammation leading to type I interferon immunopathology in severe COVID-19 disease caused by SARS-CoV-2 virus infection. Tissue damages in the lung and skin lesions are caused by activation of the cGAS-STING signaling leading to aberrant inflammation. Endothelial cell damage is also caused by activation of the cGAS-STING pathway: SARS-CoV-2 infection triggers mitochondrial DNA release into the cytosol. Released mitochondrial DNA is then detected by CGAS, leading to activation of the cGAS-STING pathway, triggering type-I interferon production and autoinflammation.

Similarity. Belongs to the STING family.

RefSeq proteins (3): NP_001288667, NP_001354187, NP_938023* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029158	STING	Family
IPR038623	STING_C_sf	Homologous_superfamily
IPR047191	STING_C_chordates	Domain
IPR055432	STING_LBD	Domain
IPR055434	STING_TM	Domain

Pfam: PF15009, PF23417

Catalyzed reactions (Rhea), 1 shown:

• H(+)(in) = H(+)(out) (RHEA:34979)

UniProt features (134 total): mutagenesis site 55, helix 19, binding site 11, strand 10, modified residue 7, sequence variant 7, topological domain 5, region of interest 4, transmembrane region 4, cross-link 4, sequence conflict 2, lipid moiety-binding region 2, chain 1, turn 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

119 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6MX3	X-RAY DIFFRACTION	1.36
4EMT	X-RAY DIFFRACTION	1.5
6UKZ	X-RAY DIFFRACTION	1.52
9CUD	X-RAY DIFFRACTION	1.53
6UKU	X-RAY DIFFRACTION	1.68
7ZKU	X-RAY DIFFRACTION	1.7
8STI	X-RAY DIFFRACTION	1.72
6MX0	X-RAY DIFFRACTION	1.73
6UKM	X-RAY DIFFRACTION	1.74
6UL0	X-RAY DIFFRACTION	1.76
6XNP	X-RAY DIFFRACTION	1.77
7KW1	X-RAY DIFFRACTION	1.8
9IJN	X-RAY DIFFRACTION	1.81
6UKV	X-RAY DIFFRACTION	1.83
9CUB	X-RAY DIFFRACTION	1.87
4QXO	X-RAY DIFFRACTION	1.88
4KSY	X-RAY DIFFRACTION	1.88
4LOI	X-RAY DIFFRACTION	1.89
8A2K	X-RAY DIFFRACTION	1.89
9KYA	X-RAY DIFFRACTION	1.89
4EMU	X-RAY DIFFRACTION	1.9
9WH8	X-RAY DIFFRACTION	1.9
6DXG	X-RAY DIFFRACTION	1.91
6UKX	X-RAY DIFFRACTION	1.93
6DNK	X-RAY DIFFRACTION	1.95
6UKY	X-RAY DIFFRACTION	1.95
8T5K	X-RAY DIFFRACTION	1.95
9CUE	X-RAY DIFFRACTION	1.95
7SSM	X-RAY DIFFRACTION	1.96
6UKW	X-RAY DIFFRACTION	1.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WV6-F1	84.13	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (11): 162; 162; 167; 167; 167; 238–241; 238; 238; 263; 263; 263

Post-translational modifications (13): 229, 241, 354, 355, 356, 358, 366, 88, 91, 20, 150, 236, 338

Mutagenesis-validated functional residues (55):

Position	Phenotype
377	does not affect ability to activate irf3.
379	does not affect ability to activate irf3.
10	abolished ability to induce the production of type i interferon.
14	abolished ability to induce the production of type i interferon.
20	does not affect amount of ubiquitination.
26	reduced homooligomerization and activation in presence of coumpond c53.
30	reduced homooligomerization and activation in presence of coumpond c53.
44	reduced homooligomerization and activation in presence of coumpond c53.
68	abolished ability to induce the production of type i interferon.
69	abolished ability to induce the production of type i interferon.
76–78	abolishes the endoplasmic reticulum location.
91	abolished inhibition by small-molecule h-151; abolished palmitoylation.
104	reduced homooligomerization and activation in presence of coumpond c53.
137	does not affect amount of ubiquitination.
150	abolishes ubiquitination, homodimerization and subsequent production of ifn-beta.
153	partially constitutively active mutant that promotes the production of type i interferon in absence of cgamp ligand.
158	constitutively active mutant that promotes the production of type i interferon in absence of cgamp ligand.
158	abolished homodimerization and activation.
158	partially constitutively active mutant that promotes the production of type i interferon in absence of cgamp ligand.
162	slight decrease in c-di-gmp-binding. renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (dmxaa) drug,
166	slight decrease in c-di-gmp-binding.
178–180	abolishes the endoplasmic reticulum location.
230	renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (dmxaa) drug, leading to activation of the sting1 p
236	loss of deubiquitination by usp44.
238–240	strong decrease in cgamp-binding without affecting interaction with tbk1. abolished ability to induce autophagy.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-1834941	STING mediated induction of host immune responses
R-HSA-3134975	Regulation of innate immune responses to cytosolic DNA
R-HSA-3249367	STAT6-mediated induction of chemokines
R-HSA-3270619	IRF3-mediated induction of type I IFN
R-HSA-6798695	Neutrophil degranulation
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-1834949	Cytosolic sensors of pathogen-associated DNA
R-HSA-5663205	Infectious disease
R-HSA-9678108	SARS-CoV-1 Infection
R-HSA-9679506	SARS-CoV Infections
R-HSA-9692914	SARS-CoV-1-host interactions
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 403 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VACUOLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_RESPONSE_TO_INTERFERON_BETA, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (30): autophagosome assembly (GO:0000045), activation of innate immune response (GO:0002218), pattern recognition receptor signaling pathway (GO:0002221), positive regulation of defense response to virus by host (GO:0002230), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), positive regulation of macroautophagy (GO:0016239), positive regulation of type I interferon production (GO:0032481), positive regulation of interferon-beta production (GO:0032728), cellular response to interferon-beta (GO:0035458), innate immune response (GO:0045087), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of inflammatory response (GO:0050727), protein complex oligomerization (GO:0051259), defense response to virus (GO:0051607), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), reticulophagy (GO:0061709), protein localization to endoplasmic reticulum (GO:0070972), cellular response to exogenous dsRNA (GO:0071360), antiviral innate immune response (GO:0140374), cGAS/STING signaling pathway (GO:0140896), immune system process (GO:0002376), monoatomic ion transport (GO:0006811), autophagy (GO:0006914), regulation of gene expression (GO:0010468), signal transduction involved in regulation of gene expression (GO:0023019), protein exit from endoplasmic reticulum (GO:0032527), monoatomic ion transmembrane transport (GO:0034220), positive regulation of cGAS/STING signaling pathway (GO:0141111), positive regulation of cytokine production involved in inflammatory response (GO:1900017), proton transmembrane transport (GO:1902600)

GO Molecular Function (13): transcription coactivator activity (GO:0003713), proton channel activity (GO:0015252), protein kinase binding (GO:0019901), ubiquitin protein ligase binding (GO:0031625), cyclic-di-GMP binding (GO:0035438), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), 2’,3’-cyclic GMP-AMP binding (GO:0061507), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein serine/threonine kinase binding (GO:0120283), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (24): Golgi membrane (GO:0000139), autophagosome membrane (GO:0000421), nucleoplasm (GO:0005654), mitochondrial outer membrane (GO:0005741), endosome (GO:0005768), autophagosome (GO:0005776), peroxisome (GO:0005777), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), cytoplasmic vesicle membrane (GO:0030659), secretory granule membrane (GO:0030667), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), serine/threonine protein kinase complex (GO:1902554), STING complex (GO:1990231), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Cytosolic sensors of pathogen-associated DNA	2
STING mediated induction of host immune responses	2
Innate Immune System	2
SARS-CoV Infections	2
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
Dengue Virus-Host Interactions	1
Immune System	1
Disease	1
Viral Infection Pathways	1
SARS-CoV-1 Infection	1
SARS-CoV-2 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
bounding membrane of organelle	3
cytoplasm	3
positive regulation of innate immune response	2
positive regulation of cytokine production	2
macroautophagy	2
positive regulation of DNA-templated transcription	2
guanyl ribonucleotide binding	2
anion binding	2
cytoplasmic vesicle	2
cytoplasmic vesicle membrane	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
activation of immune response	1
innate immune response-activating signaling pathway	1
regulation of defense response to virus by host	1
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
positive regulation of autophagy	1
regulation of macroautophagy	1
regulation of type I interferon production	1
type I interferon production	1
positive regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
response to interferon-beta	1
cellular response to cytokine stimulus	1
immune response	1
defense response to symbiont	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
protein-containing complex assembly	1

Protein interactions and networks

STRING

1611 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STING1	TBK1	Q9UHD2	980
STING1	MAVS	Q7Z434	968
STING1	CGAS	Q8N884	894
STING1	IFNB1	P01574	891
STING1	IRF3	Q14653	888
STING1	RIGI	O95786	857
STING1	NLRX1	Q86UT6	838
STING1	IFIT1	P09914	776
STING1	RNF5	Q99942	734
STING1	MFN1	Q8IWA4	687
STING1	IKBKE	Q14164	679
STING1	SSR2	P43308	675
STING1	DHX58	Q96C10	673
STING1	DDX41	Q9UJV9	673
STING1	IFNA13	P01562	645

IntAct

142 interactions, top by confidence:

A	B	Type	Score
STING1	STING1	psi-mi:“MI:0915”(physical association)	0.960
STING1	STING1	psi-mi:“MI:0407”(direct interaction)	0.960
MAVS	RIGI	psi-mi:“MI:0914”(association)	0.920
STING1	TBK1	psi-mi:“MI:0915”(physical association)	0.900
TBK1	STING1	psi-mi:“MI:0915”(physical association)	0.900
STING1	MAVS	psi-mi:“MI:0915”(physical association)	0.840
MAVS	STING1	psi-mi:“MI:0915”(physical association)	0.840
STING1	MAVS	psi-mi:“MI:0403”(colocalization)	0.840

BioGRID (395): IFI16 (Affinity Capture-Western), TMEM173 (Reconstituted Complex), TMEM173 (Affinity Capture-Western), TMEM173 (Biochemical Activity), TMEM173 (Affinity Capture-Western), TMEM173 (Co-localization), TMEM173 (Affinity Capture-Western), USP18 (Affinity Capture-Western), TMEM173 (Affinity Capture-Western), TMEM173 (Affinity Capture-Western), TMEM173 (Affinity Capture-Western), TMEM173 (Affinity Capture-Western), TMEM173 (Affinity Capture-Western), TMEM173 (Affinity Capture-Western), TMEM173 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GTQ4, A0A286YFK9, A0A291NUG3, A3PNA8, A4WCS4, A4WNL6, A6TBY2, A7HIY9, A8LMA3, B1VPE7, B4TBK3, B4UKG2, B5BCL0, B5EZL8, B5FPH7, B5R317, B5RCG1, B5XNU5, B8JDK6, B8XX90, B9KNZ3, C6DA53, O54625, P0C737, P0C738, P0C739, P0DJZ4, P0DJZ5, P0DQW1, P10306, P62816, P62817, Q00336, Q00644, Q16A98, Q1GXL5, Q28487, Q2IHR6, Q2Q5T5, Q2RP13

Diamond homologs: A0A291NUG3, A0A291NUI4, A0A291NUI5, A0A2B4SES9, A0A2B4SII1, A0A2B4SJA1, A0A2B4SJD2, A0A2B4SJZ1, A7SLZ2, A8E5V9, B8XX90, E1C7U0, E7F4N7, F1M391, P0DUE1, Q2KI99, Q3TBT3, Q86WV6, A0A0B4LFY9, P0DV10, B2LT61, B2LT62, B2LT64, B2LT65, B3Y613, B3Y614, B3Y615, B3Y618, B5T267, O60603, Q0GC71, Q0ZUL9, Q2PZH4, Q2V897, Q689D1, Q6T752, Q95LA9, Q95M53, Q9DD78, Q9DGB6

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
MAVS	“up-regulates activity”	STING1	binding
STING1	“up-regulates activity”	TBK1	binding
“Papain-like proteinase”	“down-regulates activity”	STING1	binding
TBK1	“up-regulates activity”	STING1	phosphorylation
RNF5	“down-regulates quantity by destabilization”	STING1	ubiquitination
USP21	“down-regulates activity”	STING1	deubiquitination
PPM1A	“down-regulates activity”	STING1	dephosphorylation
RNF26	“up-regulates activity”	STING1	ubiquitination
TRIM56	“up-regulates activity”	STING1	ubiquitination
MUL1	“up-regulates activity”	STING1	ubiquitination
TRIM7	“down-regulates quantity by destabilization”	STING1	ubiquitination
ULK1	“down-regulates activity”	STING1	phosphorylation
DDX41	“up-regulates activity”	STING1	binding
2’-3’-cGAMP(2-)	“up-regulates activity”	STING1	binding
MAP3K7	“up-regulates activity”	STING1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TRAF3-dependent IRF activation pathway	6	142.8×	5e-10
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	5	93.9×	1e-07
Negative regulators of DDX58/IFIH1 signaling	7	71.4×	8e-10
SARS-CoV-1 activates/modulates innate immune responses	7	59.5×	2e-09
TRAF6 mediated IRF7 activation	5	59.5×	8e-07
DDX58/IFIH1-mediated induction of interferon-alpha/beta	5	39.6×	5e-06
SARS-CoV-2 activates/modulates innate and adaptive immune responses	8	22.3×	1e-07
SARS-CoV-2 Infection	5	12.6×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of type I interferon production	6	58.8×	1e-07
type I interferon-mediated signaling pathway	6	48.0×	3e-07
antiviral innate immune response	6	31.8×	3e-06
defense response to virus	10	16.1×	1e-07
positive regulation of canonical NF-kappaB signal transduction	5	8.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

341 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	4
Uncertain significance	186
Likely benign	100
Benign	11

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
143861	NM_198282.4(STING1):c.461A>G (p.Asn154Ser)	Pathogenic
143862	NM_198282.4(STING1):c.463G>A (p.Val155Met)	Pathogenic
143863	NM_198282.4(STING1):c.439G>C (p.Val147Leu)	Pathogenic
2022271	NM_198282.4(STING1):c.851G>C (p.Arg284Thr)	Pathogenic
3383481	NM_198282.4(STING1):c.852G>C (p.Arg284Ser)	Pathogenic
1299706	NM_198282.4(STING1):c.457T>A (p.Phe153Ile)	Likely pathogenic
2584430	NM_198282.4(STING1):c.614A>G (p.Asp205Gly)	Likely pathogenic
2982257	NM_198282.4(STING1):c.616T>G (p.Cys206Gly)	Likely pathogenic
4531971	NM_198282.4(STING1):c.473G>T (p.Gly158Val)	Likely pathogenic

SpliceAI

1297 predictions. Top by Δscore:

Variant	Effect	Δscore
5:139476450:AGGTT:A	acceptor_gain	1.0000
5:139476452:GTT:G	acceptor_gain	1.0000
5:139476453:TT:T	acceptor_gain	1.0000
5:139476455:C:CC	acceptor_gain	1.0000
5:139476461:C:CT	acceptor_gain	1.0000
5:139476462:A:T	acceptor_gain	1.0000
5:139476468:A:AC	acceptor_gain	1.0000
5:139476468:A:C	acceptor_gain	1.0000
5:139477327:AC:A	donor_gain	1.0000
5:139477328:CC:C	donor_gain	1.0000
5:139477366:AGGGG:A	donor_gain	1.0000
5:139478267:TAC:T	donor_loss	1.0000
5:139478268:A:AC	donor_gain	1.0000
5:139478268:A:C	donor_loss	1.0000
5:139478268:AC:A	donor_gain	1.0000
5:139478268:ACC:A	donor_gain	1.0000
5:139478268:ACCCG:A	donor_gain	1.0000
5:139478269:C:A	donor_loss	1.0000
5:139478269:C:CA	donor_gain	1.0000
5:139478269:CC:C	donor_gain	1.0000
5:139478269:CCC:C	donor_gain	1.0000
5:139478269:CCCG:C	donor_gain	1.0000
5:139478269:CCCGC:C	donor_gain	1.0000
5:139478363:C:CT	acceptor_gain	1.0000
5:139478418:A:T	acceptor_gain	1.0000
5:139476451:GGTT:G	acceptor_gain	0.9900
5:139477366:A:AC	donor_gain	0.9900
5:139477367:G:C	donor_gain	0.9900
5:139478417:C:CT	acceptor_gain	0.9900
5:139478505:AGCT:A	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000171173 (5:139482943 A>G), RS1000233347 (5:139480289 G>A), RS1000396615 (5:139475698 C>T), RS1000623211 (5:139482558 C>G,T), RS1000975914 (5:139481568 T>C), RS1000978993 (5:139475712 G>A,T), RS1001778238 (5:139481705 C>A), RS1002125838 (5:139482151 C>T), RS1002440840 (5:139480998 C>T), RS1003038970 (5:139478166 A>G), RS1003407303 (5:139479797 A>G), RS1003484356 (5:139477924 C>T), RS1003779733 (5:139478326 T>A,C,G), RS1003847778 (5:139479412 A>T), RS1004270234 (5:139477308 C>A,T)

Disease associations

OMIM: gene MIM:612374 | disease phenotypes: MIM:615934

GenCC curated gene-disease

Disease	Classification	Inheritance
STING-associated vasculopathy with onset in infancy	Strong	Autosomal dominant
familial chilblain lupus	Supportive	Autosomal dominant

Mondo (3): STING-associated vasculopathy with onset in infancy (MONDO:0014405), autoinflammatory syndrome (MONDO:0019751), familial chilblain lupus (MONDO:0018827)

Orphanet (2): STING-associated vasculopathy with onset in infancy (Orphanet:425120), Autoinflammatory syndrome (Orphanet:93665)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000965	Cutis marmorata
HP:0000988	Skin rash
HP:0001009	Telangiectasia
HP:0001387	Joint stiffness
HP:0001508	Failure to thrive
HP:0001882	Decreased total leukocyte count
HP:0001888	Decreased total lymphocyte count
HP:0001894	Thrombocytosis
HP:0001903	Anemia
HP:0001954	Recurrent fever
HP:0002205	Recurrent respiratory infections
HP:0002206	Pulmonary fibrosis
HP:0002719	Recurrent infections
HP:0002729	Follicular hyperplasia
HP:0002789	Tachypnea
HP:0002829	Arthralgia
HP:0002923	Rheumatoid factor positive
HP:0003202	Skeletal muscle atrophy
HP:0003237	Increased circulating IgG concentration
HP:0003261	Increased circulating IgA concentration
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003593	Infantile onset
HP:0003613	Antiphospholipid antibody positivity
HP:0003623	Neonatal onset
HP:0008070	Sparse hair
HP:0008404	Nail dystrophy
HP:0010783	Erythema
HP:0011227	Elevated circulating C-reactive protein concentration

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001538_15	Immune reponse to smallpox (secreted IFN-alpha)	3.000000e-14
GCST002568_1	Esophageal squamous cell carcinoma	8.000000e-20
GCST005951_151	Body mass index	6.000000e-07
GCST008479_23	Psoriasis	2.000000e-06
GCST90006923_1	Anti-Merkel cell polyomavirus IgG seropositivity	4.000000e-10
GCST90006924_1	Merkel cell polyomavirus VP1 antibody levels	7.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004340	body mass index
EFO:0007034	seropositivity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL4523377 (SINGLE PROTEIN), CHEMBL5169087 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066843 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195525 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 18,263 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL71263	VADIMEZAN	3	5,161

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Other pattern recognition receptors

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
STING agonist 2	Agonist	8.8	pKd
ulevostinag	Agonist	8.53	pKd
2'3’-cGAMP	Agonist	8.42	pKd
compound 53 [PMID: 33038794]	Agonist	6.73	pEC50
compound 40 [PMID: 33470814]	Agonist	6.62	pEC50
ASF24	Antagonist	6.31	pIC50
MSA-2	Agonist	5.61	pEC50
MK-2118	Agonist	5.56	pEC50
SNX281	Agonist	5.39	pIC50
ZSA-215	Agonist	5.05	pEC50

Binding affinities (BindingDB)

301 measured of 399 human assays (407 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[5-[3-[[2-(3-carboxypropanoyl)-6-methoxy-1,3,5,6-tetrahydroisoindol-5-yl]oxy]propoxy]-6-methoxy-1-benzothiophen-2-yl]-4-oxobutanoic acid	IC50	0.06 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
4-[5-[3-[[2-(3-carboxypropanoyl)-4-fluoro-6-methoxy-1,3,5,6-tetrahydroisoindol-5-yl]oxy]propoxy]-4-fluoro-6-methoxy-1-benzothiophen-2-yl]-4-oxobutanoic acid	IC50	0.18 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
(2S)-4-[5-[3-[[2-[(3S)-3-carboxybutanoyl]-4-fluoro-6-methoxy-1,3,5,6-tetrahydroisoindol-5-yl]oxy]propoxy]-4-fluoro-6-methoxy-1-benzothiophen-2-yl]-2-methyl-4-oxobutanoic acid	IC50	0.19 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
4-[5-[3-[[2-(3-carboxypropanoyl)-6-methoxy-1,3,5,6-tetrahydroisoindol-5-yl]oxy]propoxy]-4-fluoro-6-methoxy-1-benzothiophen-2-yl]-4-oxobutanoic acid	IC50	0.19 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
4-[5-[3-[[2-(3-carboxypropanoyl)-4-fluoro-6-methoxy-1,3,5,6-tetrahydroisoindol-5-yl]oxy]propoxy]-4-fluoro-6-methoxy-1,3,5,6-tetrahydroisoindol-2-yl]-4-oxobutanoic acid	IC50	0.32 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
sodium (S)-4-(5-(3-((2-((S)-3-carboxylatobutanoyl)-6-methoxybenzo[b]thiophen-5-yl)oxy)propoxy)-6-methoxyisoindolin-2-yl)-2-methyl-4-oxobutanoate	IC50	0.32 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
4-[5-[3-[[2-(3-carboxylatopropanoyl)-6-methoxy-1,3,5,6-tetrahydroisoindol-5-yl]oxy]propoxy]-6-hydroxy-1-benzothiophen-2-yl]-4-oxobutanoate	IC50	0.36 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
4-[6-bromo-5-[3-[[2-(3-carboxypropanoyl)-6-methoxy-1,3,5,6-tetrahydroisoindol-5-yl]oxy]propoxy]-6,7-dihydro-1-benzothiophen-2-yl]-4-oxobutanoic acid	IC50	0.65 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
4-[5-[3-[[2-(3-carboxypropanoyl)-4-fluoro-6-methoxy-1,3-dihydroisoindol-5-yl]oxy]propoxy]-6-methoxy-1,3,5,6-tetrahydroisoindol-2-yl]-4-oxobutanoic acid	IC50	0.68 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
2-amino-9-[(1S,6R,8R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-18-fluoro-3-hydroxy-12-oxo-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2,3,4,5-tetrahydro-1H-purin-6-one	EC50	1 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
2-amino-9-[(1R,6R,8R,9S,10R,15R,17R,18S)-8-(6-aminopurin-9-yl)-9-fluoro-3,18-dihydroxy-3-oxo-12-sulfanyl-12-sulfanylidene-2,4,7,11,13-pentaoxa-16-thia-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2,3,4,5-tetrahydro-1H-purin-6-one	EC50	1 nM	US-11466047: Cyclic di-nucleotide compounds as sting agonists
9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3-oxo-12-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.05 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1R,6R,8R,9S,15R,17R)-8-(6-aminopurin-9-yl)-18-fluoro-3,9,12-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.1 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1S,6R,8R,9S,15R,17R)-8-(6-aminopurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13-pentaoxa-16-thia-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.2 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1S,6R,8R,9S,15R,17R)-8-(6-aminopurin-9-yl)-9-fluoro-3,12,18-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.3 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
2-amino-9-[(1R,6R,8R,9R,10S,17R)-8-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,9-dihydroxy-12-oxo-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2,3,4,5-tetrahydro-1H-purin-6-one	EC50	1.3 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1S,6R,8R,9S,10R,15R,17R,18S)-8-(7-aminotriazolo[4,5-d]pyrimidin-3-yl)-9,18-difluoro-12-hydroxy-3-oxo-3-sulfanyl-12-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.4 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
3-[5-carbamoyl-1-[2-[5-carbamoyl-2-(2-carboxy-4-methoxy-1-benzothiophen-3-yl)benzimidazol-1-yl]ethyl]benzimidazol-2-yl]-4-methoxy-1-benzothiophene-2-carboxylic acid	KD	1.4 nM	US-12384801: Benzothiophene, thienopyridine and thienopyrimidine derivatives for the modulation of sting
9-[(1R,6R,8R,9R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-3,9,12-trihydroxy-18-methoxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.5 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1S,6R,8R,9R,10S,15R,17R,18S)-8-(6-aminopurin-9-yl)-18-fluoro-3,9,12-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.5 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
2-amino-9- [(1R,6R,8R,9R,14S,16R,17R,18R)-17- amino-16-(6-amino-9H-purin-9-yl)- 3,11,18-trihydroxy-3,11-dioxido- 2,4,7,10,12,15-hexaoxa-3,11- diphosphatricyclo[12.2.1.16,9]octadec- 8-yl]-1,9-dihydro-6H-purin-6-one	EC50	1.6 nM	US-10738074: Cyclic di-nucleotide compounds as STING agonists
9-[(1S,6R,8R,9S,10R,15R,17R,18R)-9,18-difluoro-12-hydroxy-3-oxo-8-(6-oxo-5H-purin-9-yl)-3-sulfanyl-12-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.6 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
(2S)-4-[5-[3-[[2-(3-carboxylatopropanoyl)-6-methoxy-1,3-dihydroisoindol-5-yl]oxy]propoxy]-6-methoxy-1,3,5,6-tetrahydroisoindol-2-yl]-2-methyl-4-oxobutanoate	IC50	1.63 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
4-bromo-3-[1-[2-[2-(4-bromo-2-carboxy-1-benzothiophen-3-yl)-5-carbamoylbenzimidazol-1-yl]ethyl]-5-carbamoylbenzimidazol-2-yl]-1-benzothiophene-2-carboxylic acid	KD	1.64 nM	US-12384801: Benzothiophene, thienopyridine and thienopyrimidine derivatives for the modulation of sting
4-bromo-3-[1-[2-[2-(4-bromo-2-carboxy-7-fluoro-1-benzothiophen-3-yl)-5-carbamoylbenzimidazol-1-yl]ethyl]-5-carbamoylbenzimidazol-2-yl]-7-fluoro-1-benzothiophene-2-carboxylic acid	KD	1.65 nM	US-12384801: Benzothiophene, thienopyridine and thienopyrimidine derivatives for the modulation of sting
2-amino-9-[(1R,6R,8R,9R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-5H-purine-6-thione	EC50	1.7 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
3-[5-carbamoyl-1-[2-[5-carbamoyl-2-(2-carboxy-4-chloro-1-benzothiophen-3-yl)benzimidazol-1-yl]ethyl]benzimidazol-2-yl]-4-chloro-1-benzothiophene-2-carboxylic acid	KD	1.7 nM	US-12384801: Benzothiophene, thienopyridine and thienopyrimidine derivatives for the modulation of sting
2-amino-9-[(1S,6R,8R,9R,14R,16R,17R,18R)-16- (6-amino-9H-purin-9-yl)-17-fluoro-3,11,18- trihydroxy-3,11-dioxido-2,4,7,10,12,15-hexaoxa- 3,11-diphosphatricyclo[12.2.1.16,9]octadec-8-yl]- 1,9-dihydro-6H-purin-6-one	EC50	1.8 nM	US-10738074: Cyclic di-nucleotide compounds as STING agonists
2-amino-9-[(1R,6R,8R,9R,14R,16R,17R,18R)-16-(6-aminopurin-9-yl)-11,17,18-trihydroxy-3-oxo-3-sulfanyl-11-sulfanylidene-2,4,7,10,12,15-hexaoxa-3lambda5,11lambda5-diphosphatricyclo[12.2.1.16,9]octadecan-8-yl]-2,3,4,5-tetrahydro-1H-purin-6-one	EC50	1.9 nM	US-10738074: Cyclic di-nucleotide compounds as STING agonists
2-amino-9-[(1R,6S,8R,9R,14R,16R,17R,18R)-18-amino-16-(6-aminopurin-9-yl)-3,11,17-trihydroxy-3,11-dioxo-2,4,7,10,12,15-hexaoxa-3lambda5,11lambda5-diphosphatricyclo[12.2.1.16,9]octadecan-8-yl]-2,3,4,5-tetrahydro-1H-purin-6-one	EC50	1.9 nM	US-10738074: Cyclic di-nucleotide compounds as STING agonists
9-[(1R,6R,8R,9R,10R,15R,17R,18R)-9-fluoro-3,12,18-trihydroxy-3,12-dioxo-8-(6-oxo-5H-purin-9-yl)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	1.9 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
2-imino-9-[(1R,6R,8R,9R,10S,15R,17R,18R)-3,9,12,18-tetrahydroxy-8-(6-methylpurin-9-yl)-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-5H-purin-6-one	EC50	2 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
2-amino-9-[(1R,6R,8R,10S,15S,17R)-8-(6-aminopurin-9-yl)-3-hydroxy-12-sulfanyl-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2,3,4,5-tetrahydro-1H-purin-6-one	EC50	2 nM	US-11466047: Cyclic di-nucleotide compounds as sting agonists
2-[5-carbamoyl-1-[2-[5-carbamoyl-2-(2-carboxy-6-iodophenyl)-4-methoxybenzimidazol-1-yl]ethyl]-4-methoxybenzimidazol-2-yl]-3-iodobenzoic acid	KD	2 nM	US-12415785: Compound modulators of sting
2,2’-(Ethane-1,2-diylbis(5- carbamoyl-4-methoxy-1H- benzo[d]imidazole-1,2- diyl))bis(3-chlorobenzoic acid) Mixture of three atropisomers (meso and racemate)	KD	2 nM	US-12415785: Compound modulators of sting
1,1’-(Ethane-1,2-diyl)bis(2- (2-chloro-6-(2H-tetrazol-5- yl)phenyl)-4-methoxy-1H- benzo[d]imidazole-5- carboxamide) Mixture of atropisomers separated (meso and racemate): Peak 2 (unassigned stereochemistry)	KD	2 nM	US-12415785: Compound modulators of sting
2-amino-9-[(1R,6R,8R,9R,14S,16R,17R,18R)-16- (6-amino-9H-purin-9-yl)-17-azido-3,11,18- trihydroxy-3,11-dioxido-2,4,7,10,12,15-hexaoxa- 3,11-diphosphatricyclo[12.2.1.16,9]octadec-8-yl]- 1,9-dihydro-6H-purin-6-one	EC50	2.3 nM	US-10738074: Cyclic di-nucleotide compounds as STING agonists
9-[(1R,6R,8R,9R,10S,15S,17R,18R)-17-(2-amino-6-oxo-2,3,4,5-tetrahydro-1H-purin-9-yl)-18-azido-3,9,12-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-8-yl]-1H-purin-6-one	EC50	2.3 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1R,6S,7R,9S,15S,19R)-19-(6-aminopurin-9-yl)-4,12-dihydroxy-4,12-dioxo-3,5,8,11,13,16,18-heptaoxa-4lambda5,12lambda5-diphosphatetracyclo[13.2.2.16,9.01,14]icosan-7-yl]-2-imino-5H-purin-6-one	EC50	2.4 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1S,6R,8R,9S,15S,17R)-8-(6-aminopurin-9-yl)-9-fluoro-12-hydroxy-3-oxo-3-sulfanyl-12-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	2.4 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1R,6R,8R,9R,10S,15S,17R)-3,9-dihydroxy-12-oxo-8-(6-oxo-5H-purin-9-yl)-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	2.5 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1R,6R,8R,9R,10S,15S,17R,18R)-18-amino-8-(6-aminopurin-9-yl)-3,9,12-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	2.6 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1R,6R,8R,9R,10R,15R,17R,18R)-17-(6-aminopurin-9-yl)-9-fluoro-3,12,18-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-8-yl]-5H-purin-6-one	EC50	2.6 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1R,6R,8R,9R,10S,15S,17R)-8-(6-aminopurin-9-yl)-3,9,12-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-5H-purin-6-one	EC50	2.7 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
2-amino-9-[(1R,6R,8S,9S,14S,16S,17R,18R)-16-(6-aminopurin-9-yl)-17-azido-18-fluoro-3,11-dihydroxy-3,11-bis(sulfanylidene)-2,4,7,10,12,15-hexaoxa-3lambda5,11lambda5-diphosphatricyclo[12.2.1.16,9]octadecan-8-yl]-2,3,4,5-tetrahydro-1H-purin-6-one	EC50	2.9 nM	US-10738074: Cyclic di-nucleotide compounds as STING agonists
1-[(1R,6R,8R,9R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-3aH-imidazo[4,5-c]pyridin-4-one	EC50	3.1 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1R,6R,8S,9S,10S,15R,17R,18R)-8-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	3.2 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
4-[2-[3-[[6-(3-carboxypropanoyl)-3-methoxy-5,7-dihydropyrrolo[3,4-b]pyridin-2-yl]oxy]propoxy]-3-methoxy-5,7-dihydropyrrolo[3,4-b]pyridin-6-yl]-4-oxobutanoic acid	IC50	3.28 nM	US-20250108123: COMPOUND-LINKER CONSTRUCTS COMPRISING NOVEL COMPOUNDS USEFUL AS STING AGONISTS AND USES THEREOF
9-[(1R,6R,8R,9R,10R,15R,17R,18R)-9-fluoro-3,12,18-trihydroxy-8-(6-oxo-5H-purin-9-yl)-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	3.3 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists
9-[(1S,6R,8R,9S,15S,17R)-8-(6-aminopurin-9-yl)-9-fluoro-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-2-imino-5H-purin-6-one	EC50	3.4 nM	US-11453697: Cyclic di-nucleotide compounds as sting agonists

ChEMBL bioactivities

1865 potent at pChembl≥5 of 2343 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	Kd	0.06	nM	CHEMBL5188233
10.21	IC50	0.0623	nM	CHEMBL5201766
9.96	Kd	0.11	nM	CHEMBL4465054
9.72	Ki	0.19	nM	CHEMBL6003926
9.71	Kd	0.195	nM	CHEMBL5967512
9.70	Kd	0.2	nM	CHEMBL5197229
9.70	IC50	0.2	nM	CHEMBL5175703
9.70	Kd	0.2	nM	CHEMBL6003926
9.70	Ki	0.2	nM	CHEMBL5844854
9.70	Ki	0.2	nM	CHEMBL5911979
9.52	IC50	0.3	nM	CHEMBL5183186
9.52	Kd	0.3	nM	CHEMBL5911979
9.52	Kd	0.3	nM	CHEMBL6032593
9.52	Ki	0.3	nM	CHEMBL6032593
9.45	EC50	0.3536	nM	CHEMBL5201766
9.40	EC50	0.4	nM	CHEMBL5854415
9.36	Kd	0.44	nM	CHEMBL5827681
9.30	Kd	0.5	nM	CHEMBL6032593
9.22	IC50	0.6	nM	CHEMBL5187622
9.15	IC50	0.7	nM	CHEMBL5186267
9.11	Kd	0.78	nM	CHEMBL5844854
9.10	Kd	0.789	nM	CHEMBL5435411
9.00	EC50	1	nM	CHEMBL4764478
9.00	IC50	1	nM	CHEMBL5197904
9.00	EC50	1	nM	CHEMBL5420155
9.00	EC50	1	nM	CHEMBL5440962
9.00	EC50	1	nM	CHEMBL5404655
9.00	EC50	1	nM	CHEMBL5873892
9.00	Kd	1	nM	CHEMBL5769718
9.00	Kd	1	nM	CHEMBL5911979
9.00	Kd	1	nM	CHEMBL6003926
9.00	Ki	1	nM	CHEMBL5769718
9.00	Ki	1	nM	CHEMBL5923528
9.00	Ki	1	nM	CHEMBL6004024
9.00	EC50	1	nM	CHEMBL5942816
9.00	EC50	1	nM	CHEMBL6057948
9.00	Kd	1	nM	CHEMBL5793235
8.98	EC50	1.05	nM	CHEMBL5974695
8.98	IC50	1.05	nM	CHEMBL4465054
8.96	IC50	1.1	nM	CHEMBL5182772
8.96	IC50	1.1	nM	CHEMBL5188233
8.96	EC50	1.1	nM	CHEMBL5834306
8.92	EC50	1.2	nM	CHEMBL4465286
8.92	EC50	1.2	nM	CHEMBL5187622
8.92	IC50	1.2	nM	CHEMBL5175703
8.92	EC50	1.2	nM	CHEMBL6065500
8.92	EC50	1.2	nM	CHEMBL5812647
8.92	EC50	1.2	nM	CHEMBL5854626
8.92	EC50	1.2	nM	CHEMBL4441395
8.89	IC50	1.3	nM	CHEMBL5186267

PubChem BioAssay actives

1094 with measured affinity, of 3548 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[(E)-4-[5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-[3-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]propoxy]benzimidazol-1-yl]but-2-enyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-methoxybenzimidazole-5-carboxamide	1905663: Agonist activity at STING in human wild-type THP1-Dual cells co-expressing ISRE reporter assessed as IRF-mediated immune response incubated for 24 hrs by QUANTI Luc based microplate reader method	ec50	<0.0001	uM
1-[(E)-4-[5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-(3-morpholin-4-ylpropoxy)benzimidazol-1-yl]but-2-enyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-methoxybenzimidazole-5-carboxamide	1749716: Activation of human STING (139 to 379 residues) expressed in THP1-Blue ISG cells incubated for 24 hrs by quanti-blue SEAP reporter gene assay	ec50	0.0001	uM
2-amino-9-[(1R,6R,8R,9R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one	1905862: Binding affinity to human STING HAQ variant assessed as dissociation constant by Surface plasmon resonance assay	kd	0.0001	uM
tert-butyl N-[3-[6-carbamoyl-3-[(E)-4-[5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-methoxybenzimidazol-1-yl]but-2-enyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]benzimidazol-4-yl]oxypropyl]carbamate	1905662: Binding affinity to recombinant human His-tagged STING by measuring fluorescent signals in the presence of d2 labelled STING wild type ligand by HTRF based microplate reader analysis	ic50	0.0001	uM
2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3-hydroxy-12-oxo-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905862: Binding affinity to human STING HAQ variant assessed as dissociation constant by Surface plasmon resonance assay	kd	0.0001	uM
2-amino-9-[(1R,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9-fluoro-3,12,18-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905855: Displacement of radiolabeled [3H]-2’,3’-cGAMP from wild type human STING incubated for 2 hrs by scintillation counting method	ic50	0.0002	uM
2-amino-9-[(1R,6R,8S,9R,10S,15S,17S,18R)-8-(6-aminopurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one	1845687: Binding affinity to human STING (137 to 379 residues) assessed as dissociation constant by isothermal titration calorimetry assay	kd	0.0002	uM
2-amino-9-[(1S,6R,8R,9R,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905855: Displacement of radiolabeled [3H]-2’,3’-cGAMP from wild type human STING incubated for 2 hrs by scintillation counting method	ic50	0.0003	uM
3-[(E)-4-[5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-(3-morpholin-4-ylpropoxy)benzimidazol-1-yl]but-2-enyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]thieno[2,3-d]imidazole-5-carboxamide	1861474: Binding affinity to His6-tagged human wild type STING R232 variant by homogeneous time-resolved fluorescence assay	ic50	0.0006	uM
2-amino-9-[(1R,6R,8R,9R,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9-fluoro-3,12,18-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905855: Displacement of radiolabeled [3H]-2’,3’-cGAMP from wild type human STING incubated for 2 hrs by scintillation counting method	ic50	0.0007	uM
2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-methoxy-1-[3-[[5-[2-(trifluoromethyl)phenyl]-1,3-oxazol-2-yl]amino]propyl]benzimidazole-5-carboxamide	2030556: Binding affinity to His-tagged wild type human STING C-terminal domain (149 to 379 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by biolayer interferometry analysis	kd	0.0008	uM
1-[(E)-4-[5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-(3-hydroxypropoxy)benzimidazol-1-yl]but-2-enyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-methoxybenzimidazole-5-carboxamide	2010383: Agonist activity at STING in digitonin-permeabilized human THP1-Dual cells expressing NF-kappaB-SEAP and IRF-Lucia luciferase reporter assessed as increase in IRF-luciferase activation incubated for 24 hrs by QUANTI-Luc assay	ec50	0.0010	uM
2-amino-9-[(1R,6R,8R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-3,12,18-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one	1546612: Displacement of [3H]-cGAMP from full length STING HAQ mutant in human THP1 cells by filtration binding assay	ec50	0.0010	uM
2-amino-9-[(1R,6R,8R,9R,10S,15S,17R,18R)-8-(6-aminopurin-9-yl)-18-azido-3,9,12-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one	1546612: Displacement of [3H]-cGAMP from full length STING HAQ mutant in human THP1 cells by filtration binding assay	ec50	0.0010	uM
5-amino-3-[(1R,6R,8R,9R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-6H-triazolo[4,5-d]pyrimidin-7-one	1546612: Displacement of [3H]-cGAMP from full length STING HAQ mutant in human THP1 cells by filtration binding assay	ec50	0.0010	uM
2-amino-9-[(1R,6R,7R,9R,14S,15R,19R,20R)-19-(6-aminopurin-9-yl)-4,12,20-trihydroxy-4,12-dioxo-3,5,8,11,13,16,18-heptaoxa-4lambda5,12lambda5-diphosphatetracyclo[13.2.2.16,9.01,14]icosan-7-yl]-1H-purin-6-one	1546612: Displacement of [3H]-cGAMP from full length STING HAQ mutant in human THP1 cells by filtration binding assay	ec50	0.0010	uM
N-[5-carbamoyl-1-[(E)-4-[5-carbamoyl-2-[(4-ethyl-2-methyl-1,3-oxazole-5-carbonyl)amino]-7-(3-hydroxypropoxy)benzimidazol-1-yl]but-2-enyl]-7-methoxybenzimidazol-2-yl]-4-ethyl-2-methyl-1,3-oxazole-5-carboxamide	2010383: Agonist activity at STING in digitonin-permeabilized human THP1-Dual cells expressing NF-kappaB-SEAP and IRF-Lucia luciferase reporter assessed as increase in IRF-luciferase activation incubated for 24 hrs by QUANTI-Luc assay	ec50	0.0010	uM
2-ethyl-N-[1-[(E)-4-[2-(2-ethyl-5-methylpyrazole-3-carbonyl)imino-4-(hydroxymethyl)-3-methylbenzimidazol-1-yl]but-2-enyl]-3-methylbenzimidazol-2-ylidene]-5-methylpyrazole-3-carboxamide	1678562: Competitive binding affinity to human recombinant C-terminal Avi-tag STING using Alexa 488 probe incubated for 15 mins by FRET based assay	ic50	0.0010	uM
2-ethyl-N-[1-[(E)-4-[2-(2-ethyl-5-methylpyrazole-3-carbonyl)imino-3-methyl-7-(morpholin-4-ylmethyl)benzimidazol-1-yl]but-2-enyl]-3-methylbenzimidazol-2-ylidene]-5-methylpyrazole-3-carboxamide	1678562: Competitive binding affinity to human recombinant C-terminal Avi-tag STING using Alexa 488 probe incubated for 15 mins by FRET based assay	ic50	0.0010	uM
2-ethyl-N-[3-[(E)-4-[2-(2-ethyl-5-methylpyrazole-3-carbonyl)imino-7-(3-hydroxypropoxy)-3-methylbenzimidazol-1-yl]but-2-enyl]-4-methoxy-1-methylbenzimidazol-2-ylidene]-5-methylpyrazole-3-carboxamide	1678562: Competitive binding affinity to human recombinant C-terminal Avi-tag STING using Alexa 488 probe incubated for 15 mins by FRET based assay	ic50	0.0010	uM
N-[1-[(E)-4-[7-(1,2-dihydroxyethyl)-2-(2-ethyl-5-methylpyrazole-3-carbonyl)imino-3-methylbenzimidazol-1-yl]but-2-enyl]-3-methylbenzimidazol-2-ylidene]-2-ethyl-5-methylpyrazole-3-carboxamide	1678562: Competitive binding affinity to human recombinant C-terminal Avi-tag STING using Alexa 488 probe incubated for 15 mins by FRET based assay	ic50	0.0010	uM
2-ethyl-N-[1-[(E)-4-[2-(2-ethyl-5-methylpyrazole-3-carbonyl)imino-3-methyl-7-(piperidin-1-ylmethyl)benzimidazol-1-yl]but-2-enyl]-3-methylbenzimidazol-2-ylidene]-5-methylpyrazole-3-carboxamide	1678562: Competitive binding affinity to human recombinant C-terminal Avi-tag STING using Alexa 488 probe incubated for 15 mins by FRET based assay	ic50	0.0010	uM
N-[1-[(E)-4-[7-(azepan-1-ylmethyl)-2-(2-ethyl-5-methylpyrazole-3-carbonyl)imino-3-methylbenzimidazol-1-yl]but-2-enyl]-3-methylbenzimidazol-2-ylidene]-2-ethyl-5-methylpyrazole-3-carboxamide	1678562: Competitive binding affinity to human recombinant C-terminal Avi-tag STING using Alexa 488 probe incubated for 15 mins by FRET based assay	ic50	0.0010	uM
(1R,6R,8R,9R,10R,15R,17S,18R)-8-(6-aminopurin-9-yl)-17-ethynyl-9-fluoro-3-hydroxy-12-oxo-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-18-ol	1546612: Displacement of [3H]-cGAMP from full length STING HAQ mutant in human THP1 cells by filtration binding assay	ec50	0.0010	uM
N-[5-carbamoyl-1-[(E)-4-[5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-methoxybenzimidazol-1-yl]but-2-enyl]-7-(3-hydroxypropoxy)benzimidazol-2-yl]-4-ethyl-2-methyl-1,3-oxazole-5-carboxamide	2010383: Agonist activity at STING in digitonin-permeabilized human THP1-Dual cells expressing NF-kappaB-SEAP and IRF-Lucia luciferase reporter assessed as increase in IRF-luciferase activation incubated for 24 hrs by QUANTI-Luc assay	ec50	0.0010	uM
2-amino-9-[(1R,6R,8R,9R,10S,15S,17R)-8-(6-aminopurin-9-yl)-3,9-dihydroxy-12-oxo-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1R,6R,8R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-3,12,18-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1R,6R,7R,9R,14S,15R,19R,20R)-19-(6-aminopurin-9-yl)-4,12,20-trihydroxy-4,12-dioxo-3,5,8,11,13,16,18-heptaoxa-4lambda5,12lambda5-diphosphatetracyclo[13.2.2.16,9.01,14]icosan-7-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1S,6R,8R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-18-fluoro-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1R,6R,8R,9R,10S,15S,17R)-8-(6-aminopurin-9-yl)-3,9,12-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1R,6R,8R,9R,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9-fluoro-3,18-dihydroxy-12-oxo-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1S,6R,8R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-18-fluoro-3-hydroxy-12-oxo-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1R,6R,7R,9R,14S,15R,19R,20R)-19-(6-aminopurin-9-yl)-4,20-dihydroxy-12-oxo-12-sulfanyl-4-sulfanylidene-3,5,8,11,13,16,18-heptaoxa-4lambda5,12lambda5-diphosphatetracyclo[13.2.2.16,9.01,14]icosan-7-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1R,6S,7R,9R,14S,15R,19R,20R)-19-(6-aminopurin-9-yl)-20-fluoro-4,12-dihydroxy-4,12-dioxo-3,5,8,11,13,16,18-heptaoxa-4lambda5,12lambda5-diphosphatetracyclo[13.2.2.16,9.01,14]icosan-7-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0010	uM
2-amino-9-[(1S,6R,8R,9R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-18-fluoro-3,9,12-trihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0011	uM
2-amino-9-[(1R,6R,8R,9R,10S,15R,17R,18S)-8-(6-aminopurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13-pentaoxa-16-thia-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one	1546612: Displacement of [3H]-cGAMP from full length STING HAQ mutant in human THP1 cells by filtration binding assay	ec50	0.0012	uM
2-amino-9-[(1R,6R,8R,9R,10R,15S,17R)-8-(6-aminopurin-9-yl)-9-fluoro-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0013	uM
2-amino-9-[(1R,6R,8R,10S,15S,17R)-8-(6-aminopurin-9-yl)-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0013	uM
S-[2-[[(1S,6S,8S,10R,15R,17R)-8,17-bis(6-aminopurin-7-yl)-12-[2-(2,2-dimethylpropanoylsulfanyl)ethoxy]-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.3.0.06,10]octadecan-3-yl]oxy]ethyl] 2,2-dimethylpropanethioate	2001512: Agonist activity at STING in human THP-1 reporter cells incubated for 4 hrs in presence of lipofectamine 2000 by QUANTI-Luc assay	ec50	0.0013	uM
3-[(1R,6R,8R,9R,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9-fluoro-3,18-dihydroxy-12-oxo-12-sulfanyl-3-sulfanylidene-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-6H-imidazo[4,5-d]pyridazin-7-one	1998282: Binding affinity to recombinant human Avi-tagged wild type STING (149 to 379 residues) expressed in Escherichia coli BL21 DE3 assessed as dissociation constant by Surface plasmon resonance analysis	kd	0.0015	uM
1-[4-[5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]benzimidazol-1-yl]butyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]benzimidazole-5-carboxamide	1575520: Binding affinity to human C-terminal STING domain (143 to 379 residues) using 3H-cGAMP as substrate by high-throughput screening assay	kd	0.0016	uM
1-[(E)-4-[7-(3-aminopropoxy)-5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]benzimidazol-1-yl]but-2-enyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-methoxybenzimidazole-5-carboxamide	1905663: Agonist activity at STING in human wild-type THP1-Dual cells co-expressing ISRE reporter assessed as IRF-mediated immune response incubated for 24 hrs by QUANTI Luc based microplate reader method	ec50	0.0016	uM
2-amino-9-[(1R,6R,8R,9R,10S,15R,17R,18R)-8-(6-amino-2-fluoropurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-3H-purine-6-thione	1546612: Displacement of [3H]-cGAMP from full length STING HAQ mutant in human THP1 cells by filtration binding assay	ec50	0.0017	uM
4-[5-[3-[[2-(3-carboxy-3-methylbutanoyl)-4-fluoro-6-methoxy-1-benzothiophen-5-yl]oxy]propoxy]-4-fluoro-6-methoxy-1-benzothiophen-2-yl]-2,2-dimethyl-4-oxobutanoic acid	1855686: Displacement of cGAMP from human full length STING HAQ variant expressed in insect microsomes incubated for 16 hrs by TopCount scintillation counting method	ic50	0.0020	uM
2-amino-9-[(1R,6S,8R,9R,15R,17R,18R)-8-(9-aminoimidazo[1,2-a]purin-3-yl)-18-fluoro-12-hydroxy-3-oxo-3-sulfanyl-12-sulfanylidene-2,4,11,13,16-pentaoxa-3lambda5,12lambda5-diphosphatricyclo[13.3.0.06,9]octadecan-17-yl]-1H-purin-6-one	1546622: Inhibition of wild type STING (unknown origin)	ic50	0.0020	uM
2-amino-9-[(1R,6R,7R,9S,14S,15R,19R)-19-(6-aminopurin-9-yl)-4,12-dihydroxy-4,12-dioxo-3,5,8,11,13,16,18-heptaoxa-4lambda5,12lambda5-diphosphatetracyclo[13.2.2.16,9.01,14]icosan-7-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0024	uM
[(1R,6R,8R,9R,10R,13E,15R,17R,18R)-8,17-bis(6-aminopurin-9-yl)-9,18-difluoro-3-(octanoyloxymethoxy)-3,12-dioxo-2,4,7,11,16-pentaoxa-3lambda5,12lambda5-diphosphatricyclo[13.3.0.06,10]octadec-13-en-12-yl]oxymethyl octanoate	2138165: Agonist activity at wild type STING (unknown origin) expressed in HEK293T cells measured after 7 hrs by Bright-glo luciferase assay	ec50	0.0030	uM
2-amino-9-[(1R,6R,8R,9S,10R,15S,17R)-8-(6-aminopurin-9-yl)-9-fluoro-3,12-dihydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one;azane	1905854: Displacement of radiolabeled [3H]-2’,3’-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method	ic50	0.0034	uM
2-amino-9-[(1S,6R,8R,9R,10S,15R,17R,18R)-17-(6-aminopurin-9-yl)-3,9,12,18-tetrahydroxy-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.3.0.06,10]octadecan-8-yl]-1H-purin-6-one	1575507: Binding affinity to wild type human STING C-terminal domain (139 to 379 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetric method	kd	0.0040	uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, decreases methylation	5
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	4
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	3
Benzo(a)pyrene	increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
(+)-JQ1 compound	decreases expression	2
Nickel	increases expression	2
afuresertib	increases expression	1
RU.521	decreases reaction, increases expression	1
terbufos	decreases methylation	1
arsenite	increases methylation	1
beryllium sulfate	increases expression, increases reaction, increases phosphorylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
cyanoginosin LR	increases expression	1
esculentoside A	increases expression	1
ICG 001	affects expression	1
abrine	decreases expression	1
2-(2’-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy)acetic acid	decreases reaction, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Cannabidiol	increases expression	1
Demecolcine	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	decreases methylation	1

ChEMBL screening assays

890 unique, capped per target: 890 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4325121	Binding	Agonist activity at STING in human THP1 cells assessed as stimulation of IRF3 pathway measured after 20 hrs by luciferase reporter gene assay	Design, Synthesis, and Biological Evaluation of Amidobenzimidazole Derivatives as Stimulator of Interferon Genes (STING) Receptor Agonists. — J Med Chem

Cellosaurus cell lines

30 cell lines: 18 cancer cell line, 6 transformed cell line, 5 induced pluripotent stem cell, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1WE	IMAGINi011-A	Induced pluripotent stem cell	Female
CVCL_A8AH	THP1-Dual KO-STING	Cancer cell line	Male
CVCL_A8BD	THP1-Dual KI-mSTING	Cancer cell line	Male
CVCL_A8BF	THP1-Dual KI-hSTING-A162	Cancer cell line	Male
CVCL_A8BG	THP1-Dual KI-hSTING-H232	Cancer cell line	Male
CVCL_A8BH	THP1-Dual KI-hSTING-M155	Cancer cell line	Male
CVCL_A8BI	THP1-Dual KI-hSTING-R232	Cancer cell line	Male
CVCL_A8BJ	THP1-Dual KI-hSTING-S154	Cancer cell line	Male
CVCL_A8BL	293-Dual hSTING-A162	Transformed cell line	Female
CVCL_A8BM	293-Dual hSTING-H232	Transformed cell line	Female

Clinical trials (associated diseases)

6 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT04517253	PHASE2/PHASE3	TERMINATED	A Study of Baricitinib (LY3009104) in Adult and Pediatric Japanese Participants With NNS/CANDLE, SAVI, and AGS
NCT02974595	Not specified	RECRUITING	Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still’S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION