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| Targets |
diABZI-C2-NH2 directly binds to and activates the STING protein. As an active analogue, it binds to the STING dimer with enhanced affinity. Upon binding, STING undergoes conformational change and translocates from the ER to the Golgi, where it recruits and activates TBK1. This leads to the phosphorylation of IRF3 and subsequent induction of type I interferons (IFN-alpha/beta).
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| ln Vitro |
The scientists created linked aminobenzimidazole (ABZI) compounds, or diABZIs, by ligation approach to combine the effects of two symmetry-based ABZI compounds and improve binding to STING and cellular function. Immunocompetent animals with established syngeneic colon cancers showed robust anticancer action and full and long-lasting tumor remission when intravenous diABZI STING agonist was administered [1]. Potential target proteins from THP1 cell lysates were selectively captured using diABZI-C2-NH2, which was covalently bound on agarose beads [1].
In vitro, diABZI-C2-NH2 is an active STING agonist that modulates STING-dependent type I interferon production. The linking strategy of two symmetry-related ABZI-based compounds to create diABZIs results in enhanced binding to STING and cellular function. It has been shown to induce strong type I interferon responses in a variety of cell types. |
| ln Vivo |
In vivo, diABZI-C2-NH2 induces strong antitumor activity when administered intravenously in syngeneic colon tumor-bearing mice, leading to complete and sustained tumor regression. This demonstrates its potential as an effective immunotherapeutic agent. The covalent immobilization of diABZI-C2-NH2 onto agarose beads enables the pull-down of endogenous STING, confirming its direct target engagement.
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| Enzyme Assay |
The specific in vitro STING binding protocol utilizes a nanoBRET (bioluminescence resonance energy transfer) binding assay. HEK-293 cells expressing a STING-NanoLuc fusion protein are seeded in white 384-well plates. A tracer molecule (e.g., fluorescently-labeled diABZI) is added along with a dilution series of unlabeled diABZI-C2-NH2 (0.1 nM to 10 uM). After equilibration, BRET ratio is measured. The IC50 is calculated from the displacement curve using a non-linear regression model.
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| Cell Assay |
For in vitro cellular assays, THP-1 monocytes are treated with varying concentrations of diABZI-C2-NH2 (0.1-1000 nM) for 6 hours. Total RNA is extracted and reverse transcribed to cDNA. qPCR is performed to measure relative expression of IFNB1 (IFN-beta) and ISG15. Alternatively, cell culture supernatants are collected at 24 hours post-treatment, and human IFN-beta is quantified using a sandwich ELISA kit. EC50 values are determined from concentration-response curves.
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| Animal Protocol |
An in vivo protocol for diABZI-C2-NH2 involves a CT26 colon carcinoma syngeneic mouse model. Female BALB/c mice are injected subcutaneously in the right flank with 2×10⁵ CT26 cells. When tumors reach 50-100 mm3 (day 7-10), mice are randomized and receive intravenous (tail vein) injections of diABZI-C2-NH2 (0.3-3 mg/kg in 100 uL PBS) on days 7, 9, and 11. Tumor growth is monitored every 2-3 days. Complete tumor regression is observed in a significant proportion of treated mice.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic parameters for diABZI-C2-NH2 are not widely published. As a small-molecule STING agonist, it is expected to have moderate oral bioavailability, though it is typically administered intravenously for in vivo efficacy studies due to the potency required. The primary amine functionality may improve solubility and facilitate conjugation for probe development.
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| Toxicity/Toxicokinetics |
Specific toxicology data for diABZI-C2-NH2 is not available. As a STING agonist, the main safety concern is overstimulation of the innate immune system, potentially leading to cytokine release syndrome and systemic inflammation. Standard preclinical safety evaluation would include repeat-dose toxicity studies in rodents and non-rodents to identify the no-observed-adverse-effect level (NOAEL) and monitor for signs of autoimmunity.
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| References | |
| Additional Infomation |
diABZI-C2-NH2 is a research-grade compound and is not approved for human therapeutic use. Its discovery was reported in a major publication describing the diABZI linking strategy. This compound is a valuable tool for studying STING biology and for validating STING as a therapeutic target in cancer immunotherapy. It can be covalently immobilized onto agarose beads for pull-down assays to study STING interactions.
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| Molecular Formula |
C36H43N13O4
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|---|---|
| Molecular Weight |
721.81
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| Exact Mass |
721.356
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| CAS # |
2137975-93-8
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| PubChem CID |
131997716
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| Appearance |
White to light yellow solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
53
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| Complexity |
1290
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1N(CC)C(=CC=1C)C(NC1=NC2=C(C=CC(C(=O)N)=C2)N1CCCCN1C(NC(C2=CC(C)=NN2CC)=O)=NC2=C1C=CC(C(NCCN)=O)=C2)=O
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| InChi Key |
OFHOFLFXGGZWEH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C36H43N13O4/c1-5-48-29(17-21(3)44-48)33(52)42-35-40-25-19-23(31(38)50)9-11-27(25)46(35)15-7-8-16-47-28-12-10-24(32(51)39-14-13-37)20-26(28)41-36(47)43-34(53)30-18-22(4)45-49(30)6-2/h9-12,17-20H,5-8,13-16,37H2,1-4H3,(H2,38,50)(H,39,51)(H,40,42,52)(H,41,43,53)
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| Chemical Name |
1-[4-[5-(2-aminoethylcarbamoyl)-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]benzimidazol-1-yl]butyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]benzimidazole-5-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (138.54 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.46 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3854 mL | 6.9270 mL | 13.8541 mL | |
| 5 mM | 0.2771 mL | 1.3854 mL | 2.7708 mL | |
| 10 mM | 0.1385 mL | 0.6927 mL | 1.3854 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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