NVS-STG2

Product NameNVS-STG2
CAS3030588-01-0
MFC25H33NO5
MW427.53
EINECS
MOL File3030588-01-0.mol

Chemical Properties

Boiling point	553.5±50.0 °C(predicted)
Density	1.147±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)
storage temp.	2-8°C
solubility	DMSO: 2mg/mL, clear
pka	4.59±0.10(predicted)
form	Solid
color	White to off-white
InChIKey	CZSPKEVHLRWAFC-UHFFFAOYSA-N
SMILES	OC(C1=CC=C(NCC2=CC=C(C3(C(C)(C)C)OCC(C)(C)CO3)C=C2)C(OC)=C1)=O

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids

Usage And Synthesis

Uses

NVS-STG2 is a molecular glue that targets STINGSTING by binding to pockets between adjacent STING dimer transmembrane domains, effectively acting as a molecular glue. NVS-STGI enhances the activity of cGAMP by inducing the formation of more abundant and larger oligomers. NVS-STG2 produces antitumor activity in animal models[1][2].

Biological Activity

Potent STING allosteric agonist th at induces a STING-mediated immune responses in cells.

NVS-STG2 is a potent STING (stimulator of interferon genes) allosteric agonist (AC=5.2 μM) th at induces a STING-mediated immune responses in cells. It elicits potent antitumor activity in animal models. NVS-STG2 acts as molecular glue th at binds the transmembrane domains of the neighboring STING dimers.

in vivo

NVS-STG2 (800 μg; intratumoral injection; 3 times; days 11, 14, and 18) can significantly slow tumor growth in the MC38 tumor model of hSTING gene knock-in mice^[1].
NVS-STG2 (400 μg, 800 μg; intratumoral injection; 1 time; day 8) can induce significant dose-dependent T cell priming responses in the B16-SIY tumor model of hSTING gene knock-in mice^[1].

Animal Model:	Female C57BL/6 wild-type and hSTING knock-in mice (10-12 weeks old, 20-25 g) with MC38 flank tumors and B16-SIY flank tumors^[1]
Dosage:	800 μg, 400 μg (not specified in the article about the solvent)
Administration:	For the MC38 tumor model, intratumoral injection, 3 times, on days 11, 14, and 18. For the B16-SIY tumor model, intratumoral injection, single dose, on day 8
Result:	In the MC38 tumor model, slowed tumor growth significantly, and resulted in no significant tumor growth among 4/9 mouse during the 33-day experimental period. In the B16-SIY tumor model, exhibited a dose-dependent and significant induction of T-cell priming response. Resulted a significant increase in plasma IFNγ level at 6 h after dosing.

References

[1] Li J et al. Activation of human STING by a molecular glue-like compound. Nat Chem Biol. 2023 Oct 12. DOI:10.1038/s41589-023-01434-y
[2] Sulpizio A, et al. A new road to STING activation. Nat Chem Biol. 2023 Oct 13. DOI:10.1038/s41589-023-01455-7

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