WRG-28 是一种选择性的、细胞外作用的DDR2变构抑制剂，其IC50值为 230 nM。WRG-28 抑制肿瘤侵袭，迁移和 CAFs 的促肿瘤作用，还能抑制转移性乳腺肿瘤细胞在肺部的定植。WRG-28 也在 CAIA 小鼠模型中具有较好的缓解类风湿性关节炎活性。
| 生物活性 | WRG-28 is a selective, extracellularly actingDDR2allosteric inhibitor, with anIC50of 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]. |
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体外研究
(In Vitro) | WRG-28 (1, 2 μM; 4 h) blunts collagen I-mediated DDR2 tyrosine phosphorylation and (1 μM; 7 h) ERK activation as well as SNAIL1 protein stabilization in HEK293 cells (expressing DDR2) (IC50=286 nM)[1].
WRG-28 (1 μM; 48 h) blunts tumor cell invasion and migration by inhibiting DDR2 in BT549 and 4T1 breast cancer cells[1].
WRG-28 (1 μM; 4 days) inhibits tumor-promoting effects of CAFs[1].
WRG-28 (0.5, 1 μM; 4 h) maintains inhibitory action toward acquired DDR2 mutations that are resistant to TKIs[1].
Cell Viability Assay[1] | Cell Line: | HEK293 cells (transfected with DDR2-Flag) | | Concentration: | 0.25, 0.5, 1, 2 μM | | Incubation Time: | 4 h | | Result: | Significantly inhibited collagen I-mediated DDR2 tyrosine phosphorylation at 1 or 2μM, and with an IC>sub>50of 286 nM. |
Cell Viability Assay[1] | 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 Assay[1] | Cell Line: | BT549 and 4T1 breast cancer cells (expressing endogenous DDR2) | | Concentration: | 1 μM | | Incubation Time: | 48 h | | Result: | Inhibited DDR2 induced invasion and migration of tumor cells. |
Cell Viability Assay[1] | Cell Line: | CAF cells (with tumor organoids) | | Concentration: | 1 μM | | Incubation Time: | 4 days | | Result: | Inhibited the activity of DDR2 that supported invasion of primary tumor organoids in CAFs. |
Cell Viability Assay[1] | Cell Line: | HEK293 cells (expressing DDR2T654I) | | Concentration: | 0.5, 1 μM | | Incubation Time: | 4 h | | Result: | Inhibited phosphorylation of the DDR2T654Imutant in response to collagen I. |
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体内研究
(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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 15.62 mg/mL(38.06 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.4364 mL | 12.1820 mL | 24.3641 mL | | 5 mM | 0.4873 mL | 2.4364 mL | 4.8728 mL | | 10 mM | 0.2436 mL | 1.2182 mL | 2.4364 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 1.56 mg/mL (3.80 mM); Clear solution
此方案可获得 ≥ 1.56 mg/mL (3.80 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 15.6 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 *以上所有助溶剂都可在本网站选购。
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