General Information of This 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 1/2 (discontinued)
Click To Hide/Show 1 ADC Related to This Stage
ADC Name Antibody Antigen Payload Linker ADC Info
Plozalizumab plevistinag
Plozalizumab
C-C chemokine receptor type 2 (CCR2)
dazostinag (TAK-676)
Maleimido-caproyl-PEG8-Val-Ala-PABC
Phase 1
Click To Hide/Show 1 ADC Related to This Stage
ADC Name Antibody Antigen Payload Linker ADC Info
XMT-2056
HT-19
Receptor tyrosine-protein kinase erbB-2 (HER2)
STING agonist
Hydrophilic linker of XMT-2056
Investigative
Click To Hide/Show 11 ADC Related to This Stage
ADC Name Antibody Antigen Payload Linker ADC Info
Hu-Alpha-EGFR-172 [1]
Cetuximab
Epidermal growth factor receptor (EGFR)
IMSA172
Mc-Val-Cit-PABC
Mu-Alpha-EGFR-172 [1]
mu-alpha-EGFR
Epidermal growth factor receptor (EGFR)
IMSA172
Mc-Val-Cit-PABC
Hu-Alpha-EGFR (ACVC)-172 [1]
hu-alpha-EGFR(ACVC), cetuximab with A114C and V205C mutations
Epidermal growth factor receptor (EGFR)
IMSA172
Mc-Val-Cit-PABC
STING based antibody-drug conjugate (Exelixis) [2]
Undisclosed
Undisclosed
STING agonist
Undisclosed
CRD-5500 antibody-drug conjugate [3]
Trastuzumab
Receptor tyrosine-protein kinase erbB-2 (HER2)
CRD5500
Undisclosed
IMGS-501 [4]
IMGS-001
Programmed cell death 1 ligand 1 (PD-L1); Programmed cell death 1 ligand 2 (PDCD1LG2)
STING agonist
Undisclosed
XMT-2175 [5]
Undisclosed
Undisclosed
STING agonist
Undisclosed
XMT-2068 [5]
Undisclosed
Undisclosed
STING agonist
Undisclosed
JAB-X1800 [6]
Undisclosed
Leukocyte antigen CD37 (CD37)
STING agonist
Undisclosed
JAB-BX400 [6]
Undisclosed
Receptor tyrosine-protein kinase erbB-2 (HER2)
STING agonist
Undisclosed
STING agonist ADC [7]
Undisclosed
Undisclosed
STING agonist
Undisclosed
References
Ref 1 Tumor-targeted delivery of a STING agonist improvescancer immunotherapy. Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2214278119.
Ref 2 Exelixis and Ryvu Therapeutics Establish Exclusive License Agreement to Develop Novel STING Agonist-Based Targeted Cancer Therapies; 2022
Ref 3 CRD5500: A versatile small molecule STING agonist amenable to bioconjugation as an ADC. Cancer Res (2019) 79 (13_Supplement): LB-061.
Ref 4 Immunogenesis biopharmaceutical company product pipeline
Ref 5 Mersana biopharmaceutical company product pipeline
Ref 6 A JAB-X1800/JAB-BX400 introduction by Jacobio Pharmaceuticals.
Ref 7 F-star biotechnology company product pipeline