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上海源葉生物科技有限公司
主營產(chǎn)品： S30260異硫氰酸胍,30259鹽酸胍,嗜熱菌蛋白酶 |
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- 何小姐
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- 86-021-61559134
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- 15921386130
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- 產(chǎn)品描述： LDN193189 (DM 3189) is a selective BMP signaling inhibitor, inhibiting the transcriptional activity of ALK2 and ALK3 (IC50s: 0.8/0.8/5.3/16.7 nM for ALK1/2/3/6).
- 靶點： TGF-beta/Smad
- 體內(nèi)研究： Treatment of Ad.Cre-injected, caALK2-expressing mice with LDN-193189 (3 mg/kg i.p. every 12 h) prevented radiographic lesions at P15 in all mice examined. At P30, LDN-193189 prevented ectopic bone in approximately two-thirds of mice and attenuated lesions in the remainder, whereas at P60 LDN-193189 prevented ectopic bone in one-third of mice and attenuated lesions in the remainder. In contrast to vehicle-treated mice, LDN-193189–treated mice appeared to preserve knee and ankle joints at P30 and P60. Prolonged treatment of LDLR-/- mice with LDN-193189 was well-tolerated and potently inhibited development of atheroma, as well as associated vascular inflammation, osteogenic activity, and calcification. Treatment of SCID mice bearing MDA-PCa-118b tumors with LDN-193189 significantly reduced tumor growth.
- 細胞實驗： C2C12 cells were seeded into 96-well plates at 2,000 cells per well in DMEM supplemented with 2% FBS. We treated the wells in quadruplicate with BMP ligands and LDN-193189 or vehicle. We collected the cells after 6 d in culture in 50 μl Tris-buffered saline and 1% Triton X-100. We added the lysates to p-nitro-phenylphosphate reagent in 96-well plates for 1 h and then evaluated alkaline phosphatase activity (absorbance at 405 nm). We measured cell viability and quantity by Cell Titer Aqueous One (absorbance at 490 nm), using replicate wells treated identically to those used for alkaline phosphatase measurements
- 動物實驗： In the first experiment, SCID mice were implanted with MDA-PCa-118b tumors. After 7 days when tumors reached measurable sizes, mice were injected with LDN-193189 (3 mg/kg) or with vehicle intraperitoneally twice a day. Tumor sizes and body weights were measured weekly. Mice were injected with calcein at three days and one day prior to sacrifice. Blood was collected and tumors were weighed. A portion of the tumors were fixed in formaldehyde for micro-computed tomography, using EVS CT, or further decalcified for bone histomorphometric analysis, using the OsteoMeasure Analysis System, or flash frozen for RNA preparation. Osteocalcin in the mouse serum was determined by ELISA. In the second experiment, PCa-118b tumors were first digested with Accumax, and the isolated cells were plated overnight, digested by Accutase, resuspended in Matrigel in 1:1 ratio, and injected into SCID mice (1 × 10^6 cells/mouse) subcutaneously. Mice were treated with LDN-193189 five days post-injection
- 參考文獻：
1.Derwall M, et al. Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):613-22. 2.Yu PB, et al. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med, 2008, 14(12), 1363-1369. 3.Lee YC, et al. BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Res, 2011, 71(15), 5194-5203.
- 溶解度： H2O:Insoluble DMSO:Insoluble
- 保存條件： -20℃
- 配置溶液濃度參考：
1mg 5mg 10mg 1 mM 2.086 ml 10.43 ml 20.859 ml 5 mM 0.417 ml 2.086 ml 4.172 ml 10 mM 0.209 ml 1.043 ml 2.086 ml 50 mM 0.042 ml 0.209 ml 0.417 ml
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