Target Information
General Information of This Target
Target ID | PATR0YEYYS |
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Target Name | Stimulator of interferon genes protein (STING1) |
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Gene Name | STING1 |
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Gene ID | ||||||
Synonym | Endoplasmic reticulum interferon stimulator; Mediator of IRF3 activation; Transmembrane protein 173 |
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Sequence |
MPHSSLHPSIPCPRGHGAQKAALVLLSACLVTLWGLGEPPEHTLRYLVLHLASLQLGLLL
NGVCSLAEELRHIHSRYRGSYWRTVRACLGCPLRRGALLLLSIYFYYSLPNAVGPPFTWM LALLGLSQALNILLGLKGLAPAEISAVCEKGNFNVAHGLAWSYYIGYLRLILPELQARIR TYNQHYNNLLRGAVSQRLYILLPLDCGVPDNLSMADPNIRFLDKLPQQTGDHAGIKDRVY SNSIYELLENGQRAGTCVLEYATPLQTLFAMSQYSQAGFSREDRLEQAKLFCRTLEDILA DAPESQNNCRLIAYQEPADDSSFSLSQEVLRHLRQEEKEEVTVGSLKTSAVPSTSTMSQE PELLISGMEKPLPLRTDFS Click to Show/Hide
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Family | the STING family |
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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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Full List of The ADC Related to This Target
Phase 1
ADC Info | ADC Name | Antibody | Antigen | Payload | Linker | Ref |
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TAK-500 |
Anti-CCR2 TAK500 IgG1 mAb |
CCR2 |
STING agonist |
Maleimido-caproyl |
[1] |
Clinical candidate
ADC Info | ADC Name | Antibody | Antigen | Payload | Linker | Ref |
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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
ADC Info | ADC Name | Antibody | Antigen | Payload | Linker | Ref |
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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
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