WRG-28

Product NameWRG-28
CAS1913291-02-7
MFC21H18N2O5S
MW410.44
EINECS
MOL File1913291-02-7.mol

Chemical Properties

Boiling point	603.4±65.0 °C(Predicted)
Density	1.38±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO: 15.62 mg/mL (38.06 mM)
pka	11.55±0.50(Predicted)
form	Solid
color	Pink to red
InChIKey	AARVTLIQNGAELZ-UHFFFAOYSA-N
SMILES	[S](=O)(=O)(NCC)c1ccc(cc1)COc2cc3[o]c4c(nc3cc2)cc[c](c4)=O

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids

Usage And Synthesis

Uses

WRG-28 is a selective, extracellularly acting DDR2 allosteric inhibitor, with an IC50 of 230 nM. WRG-28 inhibits tumor invasion, migration and tumor-supporting effects of cancer-associated fibroblasts (CAFs). WRG-28 inhibits metastatic breast tumor cell colonization in the lungs. WRG-28 also shows good activity of relieving rheumatoid arthritis in CAIA model of mice[1][2].

Biological Activity

WRG-28 is a potent, selective and extracellularly acting allosteric inhibitor of discoidin domain receptor 2 (DDR2) th at potently inhibits invasion and migration in mice model of breast cancer. WRG-28 inhibits metastatic breast tumor cell colonization in the lungs.

in vivo

WRG-28 (10 mg/kg; i.v.; single) attenuates biochemical signaling of DDR2 in breast tumors in vivo^[1].
WRG-28 (10 mg/kg; i.v.; single daily for 7 days) reduces metastatic lung colonization of breast tumor cells^[1].
WRG-28 (10 mg/kg; i.v.; single daily for 21 days) decreases both the inflammatory reaction and joint destruction in mice with collagen antibody-induced arthritis (CAIA)^[2].

Animal Model:	Female BALB/cJ mice (8-week-old; 4T1-Snail-CBG tumor-bearing mice model)^[1].
Dosage:	10 mg/kg
Administration:	Intravenous injection, single.
Result:	Reduced 60% SNAIL1-clic beetle green (SNAIL1.CBG) level within the tumor in mice.

Animal Model:	Female BALB/cJ mice (8-week-old; injected with 4T1 GFP-luc expressing cells)^[1].
Dosage:	10 mg/kg
Administration:	Intravenous injection, single daily for 7 days.
Result:	Reduced lung colonization to a level comparable to shDDR2-depleted cells.

Animal Model:	Male DBA/1 mice (8-week-old; CAIA model)^[2].
Dosage:	10 mg/kg
Administration:	Intravenous injection, single daily for 21 days.
Result:	Significantly ameliorated arthritis in the mice (reduced production of IL-15 and Dkk-1), the hind- paw thickness of the mice was also reduced. Inhibited inflammatory cell infiltration and destruction of cartilage in mouse ankle and serum. Significantly alleviated bone destruction, reduced the extent of joint space enlargement and bone mineral density, as well as decreased the severity of bone loss.

IC 50

DDR2: 230 nM (IC₅₀)

References

[1] Grither WR, et al. Inhibition of tumor-microenvironment interaction and tumor invasion by small-molecule allosteric inhibitor of DDR2 extracellular domain. Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7786-E7794. DOI:10.1073/pnas.1805020115
[2] Mu N, et al. Blockade of Discoidin Domain Receptor 2 as a Strategy for Reducing Inflammation and Joint Destruction in Rheumatoid Arthritis Via Altered Interleukin-15 and Dkk-1 Signaling in Fibroblast-Like Synoviocytes. Arthritis Rheumatol. 2020 Jun;72(6):943-956. DOI:10.1002/art.41205

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