WRG-28

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

WRG-28（DDR2 抑制剂 WRG-28）是一种有效的、选择性的、盘状蛋白结构域受体 2 (DDR2) 的变构抑制剂，结合 IC50 为 230 nM。

WRG-28 (DDR2 inhibitor WRG-28) is a potent, selective, allosteric inhibitor of discoidin domain receptor 2 (DDR2) with binding IC50 of 230 nM; blunted collagen I-mediated DDR2 tyrosine phosphorylation, ERK activation, and SNAIL1 protein stabilization (IC50=286 nM) in HEK293 cells expressing DDR2, without effect on normal mammary epithelial MCF10A cells; displays no activity against collagen I-induced tyrosine phosphorylation of the related DDR1 RTK in HEK293 cells; WRG-28 inhibits DDR2-collagen interaction in an allosteric manner, inhibits tumor invasion and migration, as well as tumor-supporting roles of the stroma, and inhibits metastatic breast tumor cell colonization in the lungs.

Cell Viability Assay Cell Line:HEK293 cells (transfected with DDR2-Flag)Concentration:0.25, 0.5, 1, 2 μMIncubation Time:4 h Result:Significantly inhibited collagen I-mediated DDR2 tyrosine phosphorylation at 1 or 2μM, and with an IC>sub>50 of 286 nM.Cell Viability Assay Cell Line:HEK293 cells (transfected with DDR2-Flag) Concentration:1 μM Incubation Time:7 h Result:Inhibited collagen I-mediated ERK activation and SNAIL1 protein stabilization (IC50=286 nM).Cell Viability AssayCell Line:BT549 and 4T1 breast cancer cells (expressing endogenous DDR2) Concentration:1 μM Incubation Time:48 hResult:Inhibited DDR2 induced invasion and migration of tumor cells.Cell Viability Assay Cell Line:CAF cells (with tumor organoids)Concentration:1 μMIncubation Time:4 days Result:Inhibited the activity of DDR2 that supported invasion of primary tumor organoids in CAFs.Cell Viability AssayCell Line:HEK293 cells (expressing DDR2T654I)Concentration:0.5, 1 μM Incubation Time:4 h Result:Inhibited phosphorylation of the DDR2T654I mutant in response to collagen I.

Animal Model:Female BALB/cJ mice (8-week-old; 4T1-Snail-CBG tumor-bearing mice model).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).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).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.

DDR2 inhibitor WRG-28 | WRG28

Tyrosine Kinase

DDR

DDR

——

——

1913291-02-7

410.444

C21H18N2O5S

>98% (HPLC)

In Vitro:?DMSO : 15.62 mg/mL (38.06 mM)

O=S(C1=CC=C(COC2=CC(OC3=CC(C=CC3=N4)=O)=C4C=C2)C=C1)(NCC)=O

N-ethyl-4-(((3-oxo-3H-phenoxazin-7-yl)oxy)methyl)benzenesulfonamide

(-20℃)

With Ice Pack

≥ 2 years