MSA-2

Catalog No.S9681 Batch:S968104

Technical Data

Formula

C₁₄H₁₄O₅S

Molecular Weight

294.32

CAS No.

129425-81-6

Solubility (25°C)*

In vitro

DMSO

35 mg/mL (118.91 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

1.75mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 35 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

MSA-2 is an orally available non-nucleotide human STING agonist with antitumor activity.

Targets

STING ^[1]

In vitro

MSA-2 in solution exists as monomers and noncovalent dimers in an equilibrium that strongly favors monomers; MSA-2 monomers cannot bind STING, whereas the noncovalent MSA-2 dimers bind STING with nanomolar affinity. MSA-2 exhibits substantially higher cellular potency in an acidified tumor microenvironment than normal tissue, owing to increased cellular entry and retention combined with the inherently steep MSA-2 concentration dependence of STING occupancy.^[1]

In vivo

MSA-2 is orally available, manifesting similar oral and subcutaneous exposure in mice. In tumor-bearing mice, MSA-2 induced elevations of interferon-b in plasma and tumors by both routes of administration. Well-tolerated regimens of MSA-2 induced tumor regressions in mice bearing MC38 syngeneic tumors. In tumor models that are moderately or poorly responsive to PD-1 blockade, combinations of MSA-2 and anti-PD-1 antibody are superior in inhibiting tumor growth and prolonging survival over monotherapy.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines THP-1 cells, mouse macrophages Concentrations 20 μM, 0.16 μM-100 μM Incubation Time 5 h Method In the primary screen, THP-1 cells are incubated, in 1536-well plates, with test compounds (20 μM) in a RPMI1640-based assay medium in the presence of 5% carbon dioxide at 37°C for 5 hours. IFN-b levels are determined using an AlphaLISA assay and an EnVision Reader and expressed as percentages of IFN-b induced by cGAMP. STING binding activity of compounds is evaluated with a competitive radioligand binding assay using tritiated cGAMP and membrane embedded full-length recombinant human and mouse STING generated in insect cells. STING pathway activation by MSA-2 is assessed by Western blotting, probing phosphorylation status and total protein levels of STING, TBK-1, and IRF3 by using commercially available antibodies.
Animal Study:^{^[1]}	Animal Models C57BL/6J mice, NSG mice, BALB/c mice, nude NCr mice Dosages 25 mg/kg, 40 mg/kg, 50 mg/kg, 60 mg/kg, 80 mg/kg, 160 mg/kg Administration intra tumor injection, SC, PO

Cell Assay:^{^[1]}

Cell lines
THP-1 cells, mouse macrophages
Concentrations
20 μM, 0.16 μM-100 μM
Incubation Time
5 h
Method
In the primary screen, THP-1 cells are incubated, in 1536-well plates, with test compounds (20 μM) in a RPMI1640-based assay medium in the presence of 5% carbon dioxide at 37°C for 5 hours. IFN-b levels are determined using an AlphaLISA assay and an EnVision Reader and expressed as percentages of IFN-b induced by cGAMP. STING binding activity of compounds is evaluated with a competitive radioligand binding assay using tritiated cGAMP and membrane embedded full-length recombinant human and mouse STING generated in insect cells. STING pathway activation by MSA-2 is assessed by Western blotting, probing phosphorylation status and total protein levels of STING, TBK-1, and IRF3 by using commercially available antibodies.

Animal Study:^{^[1]}

Animal Models
C57BL/6J mice, NSG mice, BALB/c mice, nude NCr mice
Dosages
25 mg/kg, 40 mg/kg, 50 mg/kg, 60 mg/kg, 80 mg/kg, 160 mg/kg
Administration
intra tumor injection, SC, PO

References

[1] Bo-Sheng Pan, et al. Science. 2020 Aug 21;369(6506):eaba6098.

Selleck's MSA-2 has been cited by 1 publication

Structural insights into a shared mechanism of human STING activation by a potent agonist and an autoimmune disease-associated mutation [ Cell Discov, 2022, 8(1):133]	PubMed: 36513640

Structural insights into a shared mechanism of human STING activation by a potent agonist and an autoimmune disease-associated mutation [ Cell Discov, 2022, 8(1):133]

PubMed: 36513640

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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