| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Kd: 145 μM (STING)[1]
MSA-2 dimer targets the STING protein by binding to it as a non-covalent dimer, exhibiting a dissociation constant (Kd) of 145 microM. The dimeric binding mode is essential for its activity. Upon binding, MSA-2 activates the STING signaling pathway, leading to the phosphorylation of TBK1 and IRF3, and subsequent induction of type I interferons. |
|---|---|
| ln Vitro |
In vitro, MSA-2 dimer selectively activates STING with a Kd of 145 microM. It demonstrates superior permeability compared to cyclic dinucleotide STING agonists, enabling cellular entry without requiring specialized transporters. The compound induces STING-dependent IFN-beta production in a concentration-dependent manner in cell-based assays, validating its mechanism as a non-nucleotide STING agonist.
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| ln Vivo |
Overall survival is prolonged and tumor development is inhibited by MSA-2 dimer (60 mg/kg; oral; 50 days)[1]. Complete tumor regression is induced by MSA-2 dimer (40 mg/kg; subcutaneous injection; 25 days)[1]. Tumors with higher levels of proinflammatory cytokine (IFN-β) are treated with MSA-2 dimer (60 mg/kg; oral; 4 hours)[1]. Tumors have been found to contain higher quantities of MSA-2 dimer (60 mg/kg; sc; 4 hours) than plasma or other non-tumor tissues[1]. TBK1 and IR phosphorylation is induced by MSA-2 dimer (THP-1 cells). IFN-β is induced by MSA-2 dimer (10 μM and 33 μM; macrophages)[1].
In vivo, MSA-2 dimer demonstrates prolonged antitumor and immunogenic activity. At an oral dose of 60 mg/kg (4 hours), it increases pro-inflammatory cytokine (IFN-beta) levels in tumors. MSA-2 dimer (60 mg/kg; oral; 50 days) inhibits tumor development. When administered subcutaneously for 25 days, it shows sustained antitumor efficacy. These data confirm its oral bioavailability and long-term activity. |
| Enzyme Assay |
The in vitro STING binding protocol for MSA-2 dimer uses a fluorescence polarization (FP) competitive binding assay. Recombinant human STING protein (wild-type or HAQ variant) is incubated with a fluorescently labeled cyclic dinucleotide probe (1 nM) in assay buffer. Increasing concentrations of MSA-2 dimer (0.1 uM to 1 mM) are added. After a 60-minute incubation at 25degC, polarization is measured using a plate reader. The Kd value (145 uM) is calculated by fitting the competition curve using a one-site binding model.
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| Cell Assay |
For in vitro cellular assays, THP-1-Dual™ cells (expressing an IRF-inducible luciferase reporter) are seeded in 96-well plates at 5×10⁴ cells/well. The cells are treated with MSA-2 dimer at concentrations ranging from 1-200 uM (since Kd is 145 uM) for 18-24 hours. After treatment, 20 uL of supernatant is mixed with QUANTI-Luc™ substrate, and luminescence is measured on a plate reader. Alternatively, human IFN-beta in the supernatant is quantified by ELISA. EC50 values are determined from concentration-response curves.
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| Animal Protocol |
Animal/Disease Models: B16F10 tumor-bearing mice
Doses: 60 mg/kg Route of Administration: Po; 50 days Experimental Results: Inhibited tumor growth and prolonged overall survival. Animal/Disease Models: C57BL6 mice Doses: 40 mg/kg Route of Administration: Sc; 25 days Experimental Results: Induced complete tumor regression. Animal/Disease Models: C57BL6 mice Doses: 60 mg/kg Route of Administration: Po; 4 hrs (hours) Experimental Results: Increased proinflammatory cytokine (IFN-β) level in tumors. Animal/Disease Models: C57BL6 mice Doses: 50 mg/kg Route of Administration: Sc; 4 hrs (hours) Experimental Results: MSA-2 concentrations were observed in tumors than in plasma or other nontumor tissues. An in vivo efficacy protocol for MSA-2 dimer uses a CT26 colon carcinoma model. Female BALB/c mice are implanted subcutaneously with 2×10⁵ CT26 cells on day 0. When tumors reach approximately 50-100 mm3 (day 7), mice are randomized into groups (n=8-10 per group). MSA-2 dimer is formulated in 0.5% methylcellulose and administered orally by gavage at doses of 20, 40, or 60 mg/kg, once daily for 50 consecutive days. Tumor volumes are measured twice weekly with calipers. At study termination, tumors are excised and weighed, and blood is collected for plasma IFN-beta ELISA. |
| ADME/Pharmacokinetics |
As an orally active non-nucleotide STING agonist, MSA-2 dimer exhibits favorable pharmacokinetic properties. It has high oral bioavailability and good permeability across biological membranes, superior to cyclic dinucleotide STING agonists. The compound binds to STING as a non-covalent dimer, which is critical for its activity. Detailed PK parameters including T1/2, Cmax, and AUC are available in the primary literature supporting its development.
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| Toxicity/Toxicokinetics |
Specific toxicity data for MSA-2 dimer has not been published in detail. As a STING agonist, the primary safety concern is systemic inflammation due to type I interferon overproduction. However, the compound is described as "selective" and "well-tolerated" in animal models. Standard safety evaluation would include a 28-day repeat-dose oral toxicity study in rats to determine the NOAEL and evaluate potential target organ toxicity.
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| References | |
| Additional Infomation |
MSA-2 dimer is a research-grade compound and is not approved for clinical use. Its molecular formula is C43H46N8O8 with a molecular weight of 802.88. It is a selective, orally active non-nucleotide STING agonist (Kd = 145 microM) with long-term antitumor and immunogenic activity. MSA-2 dimer is bound to STING as a non-covalent dimer exhibiting higher permeability than cyclic dinucleotides. It inhibits tumor development and increases proinflammatory cytokine IFN-beta levels in tumors.
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| Molecular Formula |
C29H28O8S2
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|---|---|
| Molecular Weight |
568.66
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| Exact Mass |
568.122
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| CAS # |
2377881-92-8
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| PubChem CID |
139547051
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| Appearance |
White to yellow solid powder
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
39
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| Complexity |
827
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(C1=C(C=C2SC(C(=O)CCC(=O)O)=CC2=C1)OC)CCC1C=C2C=C(C(=O)CCC(=O)O)SC2=CC=1OC
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| InChi Key |
SSYYPCWAUQMVJQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H28O8S2/c1-36-22-14-24-18(12-26(38-24)20(30)6-8-28(32)33)10-16(22)4-3-5-17-11-19-13-27(21(31)7-9-29(34)35)39-25(19)15-23(17)37-2/h10-15H,3-9H2,1-2H3,(H,32,33)(H,34,35)
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| Chemical Name |
4-[5-[3-[2-(3-carboxypropanoyl)-6-methoxy-1-benzothiophen-5-yl]propyl]-6-methoxy-1-benzothiophen-2-yl]-4-oxobutanoic acid
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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) |
DMSO: 70 mg/mL (123.10 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.75 mg/mL (3.08 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 17.5 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: 1.75 mg/mL (3.08 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 17.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.75 mg/mL (3.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7585 mL | 8.7926 mL | 17.5852 mL | |
| 5 mM | 0.3517 mL | 1.7585 mL | 3.5170 mL | |
| 10 mM | 0.1759 mL | 0.8793 mL | 1.7585 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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