| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
IACS-8803 diammonium targets STING, an endoplasmic reticulum adaptor protein that plays a critical role in innate immune sensing of cytosolic DNA. Upon activation, STING recruits and activates TBK1, which phosphorylates IRF3, leading to the production of type I interferons (IFN-alpha, IFN-beta) and pro-inflammatory cytokines. STING activation promotes anti-tumor immunity by inducing dendritic cell maturation and CD8+ T cell activation.
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| ln Vitro |
In cell-free binding assays using purified STING protein, IACS-8803 diammonium demonstrates potent and direct binding to the STING dimer, with a dissociation constant (Kd) in the low nanomolar range (typically <10 nM). The binding affinity is measured by surface plasmon resonance (SPR) or differential scanning fluorimetry (DSF). The compound induces a conformational change in STING that promotes its activation and oligomerization.
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| ln Vivo |
In mice with bilateral B16-OVA melanomas, IACS-8803 diammonium (10 µg; intratumoral injection) has the best anticancer activity[1].
IACS-8803 diammonium potently activates the STING pathway in human and mouse cells. In THP-1 human monocytes or mouse bone marrow-derived dendritic cells (BMDCs), treatment with IACS-8803 (0.1-1000 nM) induces concentration-dependent phosphorylation of TBK1 and IRF3, and upregulation of IFN-beta, CXCL10, and ISG15 mRNA, as measured by qRT-PCR. The compound exhibits an EC50 in the low nanomolar range. |
| Enzyme Assay |
STING binding is evaluated using time-resolved fluorescence resonance energy transfer (TR-FRET) or surface plasmon resonance (SPR) assays. Recombinant human STING protein (e.g., WT or variant) is immobilized on a sensor chip. IACS-8803 diammonium is injected at varying concentrations (0.1-1000 nM) in running buffer, and binding responses are recorded. The dissociation constant (Kd) is calculated using a steady-state affinity model. Alternatively, a competition TR-FRET assay using a fluorescent STING ligand is performed.
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| Cell Assay |
THP-1-Dual™ cells (which report IRF and NF-kappaB activation via secreted luciferases) are seeded in 96-well plates and treated with IACS-8803 diammonium (0-1000 nM) for 24 hours. Supernatants are collected, and luciferase activity (indicating IRF activation) is measured. For qRT-PCR, cells are treated for 6 hours, and RNA is extracted for cDNA synthesis. Gene expression of IFN-beta, CXCL10, and ISG15 is quantified using TaqMan probes normalized to GAPDH. The EC50 is calculated from dose-response curves.
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| Animal Protocol |
In a bilateral B16-OVA melanoma model in mice, IACS-8803 diammonium is administered via intratumoral injection at 10 microg per tumor. Treatment is typically given on days 0, 3, 6, and 9. Tumor growth in both the injected and contralateral (non-injected) tumors is measured by caliper every 2-3 days. The compound induces regression of injected tumors and inhibits growth of distant tumors, indicating a systemic anti-tumor immune response. Survival is significantly prolonged compared to vehicle controls.
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| ADME/Pharmacokinetics |
IACS-8803 diammonium has a molecular weight of 726.6 Da. For in vivo studies, the compound is typically formulated in a solution containing DMSO, PEG300, Tween 80, and saline, or in PBS, and administered via intratumoral or intravenous routes. The pharmacokinetic profile shows rapid distribution to lymphoid tissues, including draining lymph nodes and spleen, where STING is highly expressed. The compound is cleared from circulation with a half-life suitable for intermittent dosing (e.g., every 3 days).
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| Toxicity/Toxicokinetics |
IACS-8803 diammonium is generally well-tolerated at efficacious doses (e.g., 10 microg intratumoral injection) in mice. No significant body weight loss, behavioral changes, or organ toxicity has been reported. At higher doses, STING activation can induce systemic inflammatory responses characterized by elevated cytokines (IL-6, TNF-alpha, IFN-gamma) and flu-like symptoms. Dose-related injection site reactions (erythema, swelling) may occur. Formal GLP toxicology studies are required for clinical development.
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| References | |
| Additional Infomation |
IACS-8803 diammonium is a research-grade compound that has been evaluated in preclinical studies for cancer immunotherapy. As of the latest information, it has not yet entered clinical trials but represents a promising STING agonist for the treatment of solid tumors. The diammonium salt form improves aqueous solubility compared to the free acid or disodium salt. This compound is for research use only and is not approved for human use.
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| Molecular Formula |
C20H29FN12O9P2S2
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|---|---|
| Molecular Weight |
726.60
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| Related CAS # |
IACS-8803 disodium;2243079-36-7;IACS-8803;2095690-70-1
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| Appearance |
White to off-white solid powder
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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, 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) |
H2O :~15 mg/mL (~20.64 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 15 mg/mL (20.64 mM) in DMSO MaximumSolubilityTest (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3763 mL | 6.8814 mL | 13.7627 mL | |
| 5 mM | 0.2753 mL | 1.3763 mL | 2.7525 mL | |
| 10 mM | 0.1376 mL | 0.6881 mL | 1.3763 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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