MSA 2

MSA 2 is a non-nucleotide STING agonist. It exhibits antitumor activity and stimulates interferon-β secretion in tumors. MSA 2 induces tumor regression with durable antitumor immunity, and synergizes with anti-PD-1 in syngeneic mouse tumor models. It is also orally bioavailable. Non-nucleotide STING agonist (EC50 values are 8.3 and 24 μM for human STING isoforms WT and HAQ, respectively). Exhibits antitumor activity and stimulates interferon-β secretion in tumors. Induces tumor regression with durable antitumor immunity, and synergizes with anti-PD-1 in syngeneic mouse tumor models. Orally bioavailable.

Product information

CAS Number: 129425-81-6

Molecular Weight: 294.32

Formula: C14H14O5S

Synonym:

MSA2

MSA-2

Chemical Name: 4-(5,6-dimethoxybenzo[b]thiophen-2-yl)-4-oxobutanoic acid

Smiles: COC1=CC2SC(=CC=2C=C1OC)C(=O)CCC(O)=O

InChiKey: APCLRHPWFCQIMG-UHFFFAOYSA-N

InChi: InChI=1S/C14H14O5S/c1-18-10-5-8-6-13(9(15)3-4-14(16)17)20-12(8)7-11(10)19-2/h5-7H,3-4H2,1-2H3,(H,16,17)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 59 mg/mL(200.46 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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.

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.

References:

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

Products are for research use only. Not for human use.