7x9q

Crystal structure of human STING complexed with compound BSP16

spinqualitylabelsall models 7x9q, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7x9q is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: A9X Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function STING_HUMAN 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 recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. 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). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway. Publication Abstract from PubMed Activation of the stimulator of interferon genes (STING) pathway to achieve antitumor response is an attractive approach for cancer immunotherapy. In this study, we report the identification of BSP16 (LF250) as a potent, orally available STING agonist. BSP16 strongly activates STING signaling in human and mouse cells and binds STING as a homodimer. A 2.4 A cocrystal structure revealed that BSP16 could induce the "closed" conformation of STING. In vivo studies revealed that BSP16 is well tolerated, has an excellent pharmacokinetic profile as an oral drug, and induces tumor regression and durable antitumor immunity. The promising bioactivities of BSP16 make it valuable for further development as an antitumor agent. Discovery of Selenium-Containing STING Agonists as Orally Available Antitumor Agents.,Feng X, Pan L, Qian Z, Liu D, Guan X, Feng L, Song B, Xu X, Tan N, Ma Y, Li Z, Wang Z, Bian J J Med Chem. 2022 Sep 7. doi: 10.1021/acs.jmedchem.2c00634. PMID:36069713 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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