MSA-2 dimer is a selective and orally bioactive non-nucleotide STING agonist (Kd=145 μM) with long-term anti-tumor and immunogenic activity. The MSA-2 dimer binds to STING as a non-covalent dimer with a higher permeability than circulating dinucleotides.

Physicochemical Properties

Molecular Formula	C29H28O8S2
Molecular Weight	568.66
Exact Mass	568.122
CAS #	2377881-92-8
PubChem CID	139547051
Appearance	White to yellow solid powder
LogP	5.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	14
Heavy Atom Count	39
Complexity	827
Defined Atom Stereocenter Count	0
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
InChi Key	SSYYPCWAUQMVJQ-UHFFFAOYSA-N
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)
Chemical Name	4-[5-[3-[2-(3-carboxypropanoyl)-6-methoxy-1-benzothiophen-5-yl]propyl]-6-methoxy-1-benzothiophen-2-yl]-4-oxobutanoic acid
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	Kd: 145 μM (STING)[1]
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].
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.
References	[1]. An orally available non-nucleotide STING agonist with antitumor activity. Science. 2020;369(6506):eaba6098.

Solubility Data

Solubility (In Vitro)

DMSO: 70 mg/mL (123.10 mM)

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. 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. 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 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	1.7585 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.