| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
IACS-8803 disodium targets the STING protein, an adaptor molecule in the cytosol that recognizes cyclic dinucleotides. Upon binding, IACS-8803 activates STING, leading to the phosphorylation of TBK1 and IRF3. This activation triggers the production of type I interferons (IFN-alpha and IFN-beta) and pro-inflammatory cytokines, which are crucial for initiating anti-tumor immune responses.
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| ln Vitro |
IACS-8803 disodium is a novel and highly potent STING agonist that shows robust activation of the STING pathway in vitro. It has been shown to stimulate the phosphorylation of key downstream signaling molecules including TBK1 and IRF3 in a concentration-dependent manner. This leads to the secretion of type I interferons and other inflammatory cytokines from treated cells.
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| ln Vivo |
Mice with bilateral B16-OVA melanomas have enhanced anticancer activity when administered intratumorally with IACS-8803 (10 µg)[1].
In vivo, IACS-8803 disodium demonstrates superior systemic anti-tumor response in murine models. Specifically, IACS-8803 at 10 ug via intra-tumoral injection shows superior anti-tumor activity in mice bearing bilateral B16-OVA melanomas. It exhibits robust systemic anti-tumor efficacy, making it a promising candidate for cancer immunotherapy research. |
| Enzyme Assay |
The in vitro STING binding protocol typically uses a fluorescence polarization competition assay. Recombinant human STING protein (residues 139-344) is incubated with a fluorescently-labeled cyclic dinucleotide probe (e.g., FITC-2‘3'-cGAMP). IACS-8803 disodium is serially diluted (0.1-1000 nM) and added to the reaction. After 30 minutes at room temperature, the polarization signal is read on a plate reader. The IC50 is calculated by fitting the competition curve.
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| Cell Assay |
For in vitro cellular assays, THP-1-Dual™ cells (THP-1 cells stably transfected with an IRF-inducible luciferase reporter) are seeded in 96-well plates. Cells are treated with IACS-8803 disodium at concentrations ranging from 0.01 nM to 1 uM for 18 hours. After incubation, 20 uL of supernatant is mixed with QUANTI-Luc™ substrate, and luciferase activity is measured. IFN-beta production in the supernatant is also quantified by ELISA.
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| Animal Protocol |
An in vivo efficacy protocol uses a B16-OVA syngeneic melanoma model. Female C57BL/6 mice (6-8 weeks old) are implanted subcutaneously with 5×10⁵ B16-OVA cells. When tumors reach a volume of 80-100 mm3 (typically day 7), mice receive intratumoral (i.t.) injections of IACS-8803 disodium (10 ug in 30 uL PBS) on days 7, 9, 11, and 14. Tumor volumes are measured every 3 days with calipers. On day 21, spleens and tumors are collected for flow cytometry analysis of CD8+ T-cell activation.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for IACS-8803 disodium is limited. As a cyclic dinucleotide analog, it is expected to have a short plasma half-life due to rapid clearance and enzymatic degradation by phosphodiesterases. For in vivo studies, it is typically administered by intratumoral or intravenous injection to maximize local exposure. The disodium salt formulation enhances solubility in aqueous buffers.
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| Toxicity/Toxicokinetics |
Specific toxicology data for IACS-8803 disodium has not been published. As a STING agonist, the primary safety concern is potential systemic inflammation due to excessive type I interferon production. Standard preclinical safety assessment would involve a 7-14 day repeat-dose toxicity study in rodents to determine the maximum tolerated dose (MTD) and evaluate potential cytokine release syndrome.
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| References | |
| Additional Infomation |
IACS-8803 disodium is a research-grade compound and is not approved for clinical use. Its molecular formula is C20H21FN10Na2O9P2S2 with a molecular weight of 780.48. It is a highly potent cyclic dinucleotide STING agonist with a robust systemic anti-tumor efficacy. This compound is for laboratory research purposes only and is a valuable tool for cancer immunotherapy studies.
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| Molecular Formula |
C20H23FN10O9P2S2.2NA
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|---|---|
| Molecular Weight |
716.53
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| Exact Mass |
736.018
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| CAS # |
2243079-36-7
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| Related CAS # |
IACS-8803 diammonium;IACS-8803;2095690-70-1
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| PubChem CID |
171360943
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
20
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
46
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| Complexity |
1180
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| Defined Atom Stereocenter Count |
7
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| SMILES |
OC1([H])[C@@]2([H])CO[P@](O[C@@]3([H])[C@@H](F)[C@H](N4C=NC5=C(N=CN=C45)N)O[C@]3([H])CO[P@](S)(=O)O[C@@]1([H])[C@H](N1C=NC3=C(N=CN=C13)N)O2)(S)=O.[NaH]
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| InChi Key |
RTFZBFRTZGEDLP-WCYZRWMMSA-L
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| InChi Code |
InChI=1S/C20H23FN10O9P2S2.2Na/c21-9-13-8(38-19(9)30-5-28-10-15(22)24-3-26-17(10)30)2-36-42(34,44)40-14-12(32)7(1-35-41(33,43)39-13)37-20(14)31-6-29-11-16(23)25-4-27-18(11)31;;/h3-9,12-14,19-20,32H,1-2H2,(H,33,43)(H,34,44)(H2,22,24,26)(H2,23,25,27);;/q;2*+1/p-2/t7-,8-,9-,12?,13-,14-,19-,20-,41?,42?;;/m1../s1
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| Chemical Name |
disodium;(1R,6R,8R,9R,10R,15R,17R)-8,17-bis(6-aminopurin-9-yl)-9-fluoro-12-oxido-3-oxo-12-sulfanylidene-3-sulfido-2,4,7,11,13,16-hexaoxa-3λ5,12λ5-diphosphatricyclo[13.2.1.06,10]octadecan-18-ol
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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) |
H2O: 56.67 mg/mL (76.74 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (67.70 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3956 mL | 6.9781 mL | 13.9561 mL | |
| 5 mM | 0.2791 mL | 1.3956 mL | 2.7912 mL | |
| 10 mM | 0.1396 mL | 0.6978 mL | 1.3956 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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