General Information of This Target
Target ID
PATR0YEYYS
Target Name
Stimulator of interferon genes protein (STING1)
Gene Name
STING1
Gene ID
340061
Synonym
Endoplasmic reticulum interferon stimulator; Mediator of IRF3 activation; Transmembrane protein 173
Sequence
MPHSSLHPSIPCPRGHGAQKAALVLLSACLVTLWGLGEPPEHTLRYLVLHLASLQLGLLL
NGVCSLAEELRHIHSRYRGSYWRTVRACLGCPLRRGALLLLSIYFYYSLPNAVGPPFTWM
LALLGLSQALNILLGLKGLAPAEISAVCEKGNFNVAHGLAWSYYIGYLRLILPELQARIR
TYNQHYNNLLRGAVSQRLYILLPLDCGVPDNLSMADPNIRFLDKLPQQTGDHAGIKDRVY
SNSIYELLENGQRAGTCVLEYATPLQTLFAMSQYSQAGFSREDRLEQAKLFCRTLEDILA
DAPESQNNCRLIAYQEPADDSSFSLSQEVLRHLRQEEKEEVTVGSLKTSAVPSTSTMSQE
PELLISGMEKPLPLRTDFS

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Family
the STING family
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, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol. Upon binding of c-di-GMP 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. 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. 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. 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. 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).(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.

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Uniprot Entry
STING_HUMAN
HGNC ID
HGNC:27962
KEGG ID
hsa:340061
Full List of The ADC Related to This Target
Phase 1
Click To Hide/Show 1 ADC Related to This Stage
ADC Info ADC Name Antibody Antigen Payload Linker Ref
TAK-500
Anti-CCR2 TAK500 IgG1 mAb
CCR2
STING agonist
Maleimido-caproyl
[1]
Clinical candidate
Click To Hide/Show 6 ADC Related to This Stage
ADC Info ADC Name Antibody Antigen Payload Linker Ref
IMGS-501
IMGS-001
CD274; PDCD1LG2
STING agonist
Undisclosed
[2]
XMT-2175
Undisclosed
Undisclosed
STING agonist
Undisclosed
[3]
XMT-2068
Undisclosed
Undisclosed
STING agonist
Undisclosed
[3]
JAB-X1800
Undisclosed
NT5E
STING agonist
Undisclosed
[4]
JAB-BX400
Undisclosed
ERBB2
STING agonist
Undisclosed
[4]
STING agonist ADC
Undisclosed
Undisclosed
STING agonist
Undisclosed
[5]
Investigative
Click To Hide/Show 5 ADC Related to This Stage
ADC Info ADC Name Antibody Antigen Payload Linker Ref
Hu-Alpha-EGFR-172
Cetuximab
EGFR
IMSA172
Mc-Val-Cit-PABC
[6]
Mu-Alpha-EGFR-172
mu-alpha-EGFR
EGFR
IMSA172
Mc-Val-Cit-PABC
[6]
Hu-Alpha-EGFR (ACVC)-172
hu-alpha-EGFR(ACVC), cetuximab with A114C and V205C mutations
EGFR
IMSA172
Mc-Val-Cit-PABC
[6]
STING based antibody-drug conjugate (Exelixis)
Undisclosed
Undisclosed
STING agonist
Undisclosed
[7]
CRD-5500 antibody-drug conjugate
Trastuzumab
ERBB2
CRD5500
Undisclosed
[8]
References
Ref 1 First-in-human study of TAK-500, a novel STING agonist immune stimulating antibody conjugate (ISAC), alone and in combination with pembrolizumab in patients with select advanced solid tumors. Cancer Res (2022) 82 (12_Supplement): CT249.
Ref 2 Immunogenesis biopharmaceutical company product pipeline
Ref 3 Mersana biopharmaceutical company product pipeline
Ref 4 A JAB-X1800/JAB-BX400 introduction by Jacobio Pharmaceuticals.
Ref 5 F-star biotechnology company product pipeline
Ref 6 Tumor-targeted delivery of a STING agonist improvescancer immunotherapy. Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2214278119.
Ref 7 Exelixis and Ryvu Therapeutics Establish Exclusive License Agreement to Develop Novel STING Agonist-Based Targeted Cancer Therapies; 2022
Ref 8 CRD5500: A versatile small molecule STING agonist amenable to bioconjugation as an ADC. Cancer Res (2019) 79 (13_Supplement): LB-061.

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