| Identification | Back Directory | [Name]
diABZI STING agonist-1 trihydrochloride | [CAS]
2138299-34-8 | [Synonyms]
di-ABZI
STING?agonist?diABZ
diABZI STING agonist-1
STING agonist-1 trihydrochloride
diABZI STING Agonist 3 (hydrochloride)
diABZI STING agonist-1 trihydrochloride
STING agonist-1（compound 3）trihydrochloride
inhibit,diABZI STING agonist1 trihydrochloride,MPYS,diABZI STING agonist-1 trihydrochloride,ERIS,STING,Inhibitor,MITA,Stimulator of Interferon Genes,TMEM173,diABZI STING agonist 1 trihydrochloride
(E)-1-(4-(5-Carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-methoxy-1H-benzimidazole-5-carboxamide tris(hydrochloride)
1-[(2E)-4-[5-(Aminocarbonyl)-2-[[(1-ethyl-3-methyl-1H-pyrazol-5-yl)carbonyl]amino]-7-methoxy-1H-benzimidazol-1-yl]-2-buten-1-yl]-2-[[(1-ethyl-3-methyl-1H-pyrazol-5-yl)carbonyl]amino]-7-[3-(4-morpholinyl)propoxy]-1H-benzimidazole-5-carboxamide Hydrochloride (1:3) | [Molecular Formula]
C42H52ClN13O7 | [MDL Number]
MFCD31746912 | [MOL File]
2138299-34-8.mol | [Molecular Weight]
886.41 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 50 mg/ml | [form ]
A crystalline solid | [color ]
White to yellow | [InChIKey]
PSJURLIZOBGEGB-HRNDJLQDSA-N | [SMILES]
C(N1C(=NC2=CC(C(=O)N)=CC(OCCCN3CCOCC3)=C12)NC(C1=CC(C)=NN1CC)=O)/C=C/CN1C(=NC2=CC(C(=O)N)=CC(OC)=C12)NC(C1=CC(C)=NN1CC)=O.Cl |
| Hazard Information | Back Directory | [Description]
diABZI STING agonist-1 is an agonist of the stimulator of interferon genes (STING) pathway. It induces secretion of IFN-β in human peripheral blood mononuclear cells (PBMCs; EC50 = 130 nM). diABZI STING agonist-1 (2.5 mg/kg) increases serum levels of IFN-β, IL-6, TNF, and KC/GROα in wild-type, but not Sting-/-, mice. It inhibits the cytopathic effect of the common cold human coronavirus 229E (HCoV-229E) in infected MRC-5 cells (EC50 = 3 nM). diABZI STING agonist-1 also decreases the level of severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA in primary human bronchial airway epithelial cells in an air-liquid interface assay. It decreases tumor volume and increases survival in a CT26 murine colorectal cancer model when administered at a dose of 3 mg/kg. | [Uses]
1-[(2E)-4-[5-(Aminocarbonyl)-2-[[(1-ethyl-3-methyl-1H-pyrazol-5-yl)carbonyl]amino]-7-methoxy-1H-benzimidazol-1-yl]-2-buten-1-yl]-2-[[(1-ethyl-3-methyl-1H-pyrazol-5-yl)carbonyl]amino]-7-[3-(4-morpholinyl)propoxy]-1H-benzimidazole-5-carboxamide Hydrochloride (1:3), an amino acid derivatve used in preparation of STING protein. | [in vivo]
diABZI STING agonist-1 trihydrochloride (subcutaneous injection; 2.5 mg/kg) induces STING-dependent activation of type-I interferon and pro-inflammatory cytokines in vivo[1].
diABZI STING agonist-1 trihydrochloride (intravenous injection; 3 mg/kg) exhibits systemic exposure with a half-life of 1.4 h and achieves systemic concentrations greater than the half-maximal effective concentration (EC50) for mouse STING (200 ng/ml)[1].
diABZI STING agonist-1 trihydrochloride (intravenous injection; 1.5 mg/kg; days 1, 4 and 8; 43 days) results in significant tumour growth inhibition and significantly improves survival (P < 0.001) with 8 out of 10 mice remaining tumor free at the end of the study on day 43[1]. | Animal Model: | Wild and Sting?/? C57Blk6 mice[1] | | Dosage: | 2.5 mg/kg | | Administration: | Subcutaneous injection; 2.5 mg/kg | | Result: | Activated secretion of IFNβ, IL-6, TNF, and CXCL1 in wild-type but not Sting?/? mice. |
| Animal Model: | Syngeneic mouse model of colorectal tumours (CT-26) in BALB/c mice[1] | | Dosage: | 3 mg/kg | | Administration: | Intravenous injection; 3 mg/kg | | Result: | Exhibited a half-life of 1.4 hours and achieved systemic concentrations greater than EC50 for mouse STING (200 ng/ml). |
| Animal Model: | Syngeneic mouse model of colorectal tumours (CT-26) in BALB/c mice[1] | | Dosage: | 1.5 mg/kg | | Administration: | Intravenous injection; 1.5 mg/kg; 43 days | | Result: | Resulted in significant tumour growth inhibition and improved survival. |
| [References]
[1] JOSHI M. RAMANJULU. Design of amidobenzimidazole STING receptor agonists with systemic activity[J]. Nature, 2018, 564 7736: 439-443. DOI: 10.1038/s41586-018-0705-y
[2] QINGYUAN ZHU . Inhibition of coronavirus infection by a synthetic STING agonist in primary human airway system[J]. Antiviral research, 2021, 187: Article 105015. DOI: 10.1016/j.antiviral.2021.105015
[3] ZILAN SONG. Structure–Activity Relationship Study of Amidobenzimidazole Analogues Leading to Potent and Systemically Administrable Stimulator of Interferon Gene (STING) Agonists[J]. Journal of Medicinal Chemistry, 2021, 64 3: 1649-1669. DOI: 10.1021/acs.jmedchem.0c01900 |
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