| 名稱 | Dorsomorphin |
| 描述 | Dorsomorphin (BML-275) is an AMPK inhibitor (Ki=109 nM) that is selective and ATP-competitive. Dorsomorphin inhibits the BMP type I receptors ALK2, ALK3, and ALK6. Dorsomorphin induces autophagy, and possesses antitumor activity. |
| 細(xì)胞實(shí)驗(yàn) | Dorsomorphin is dissolved in DMSO (10 mM) and stored,and then diluted with appropriate media (DMSO 0.5%) before use[2].HeLa and 786-O cells are treated with various concentrations of Dorsomorphin (0,0.3,1,3,10 μM ),Versipelostatin and Phenformin in the presence or absence of 10 mM 2DG or 1 μg/mL of Tunicamycin as a stressor for 30 h in 96-well plates.For the combination study,786-O cells are treated with various concentrations of UPR inhibitors in the presence or absence of 10 mM 2DG for 24 h.The medium is then replaced with fresh growth medium,and cells are cultured for a further 15 h.Subsequently,MTT is added to the culture medium,and the absorbance of each well is determined.For the viability assay under glucose-withdrawal conditions,HT1080 cells are treated with various concentrations of Dorsomorphin and phenformin in 12-well plates in the presence or absence of glucose for 18 h,seeded in 96-well plates with growth medium,and then cultured for a further 48 h before MTT is added.Relative cell survival (mean±SD of quadruplicate determinations) is calculated by setting each control absorbance from untreated cells as 100%.The effects of drug combinations at concentrations producing 80% cell growth inhibition (IC80) are analyzed using the isobologram method[2]. |
| 激酶實(shí)驗(yàn) | HT1080 cells are seeded in 24-well plates (2×104 cells per well) and treated with Dorsomorphin in the presence or absence of glucose or 10 mM 2DG for 2 h. HT1080 cells that overexpressed the wild-type and dominant negative AMPKα1 are prepared by transfecting plasmid DNA (pAMPKα1-wt, pAMPKα1-D168A and pcFlag as a control) in 6-well plates, seeding in 24-well plate and treating with UPR inhibitors. Cells are lysed with cell lysis buffer (20 mM Tris-HCl, pH 7.5, 250 mM NaCl, 10% glycerol, 0.5% NP-40, 1 mM EDTA, 1 mM EGTA, 0.2 mM PMSF, 1 μg/mL pepstatin, 0.5 μg/mL leupeptin, 5 mM NaF, 2 mM Na3Vo4, 2 mM β-glycerophosphate, 1 mM DTT). Relative AMPK kinase activity (mean±SD of duplicate determinations) to control sample (vehicle or pcFlag under normal growth conditions) is determined using the CycLex AMPK kinase assay kit[2]. |
| 體外活性 | 方法：人腫瘤細(xì)胞 HeLa 和 HCT116 用 Dorsomorphin (1.25-80 μM) 處理 24 h，使用 CCK-8 方法檢測(cè)細(xì)胞活力。
結(jié)果：Dorsomorphin 抑制 HeLa 和 HCT116 細(xì)胞的活力，IC50 值分別為 10.71 μM 和 11.34 μM。[1]
方法：ATL 患者來(lái)源的 PBMCs 細(xì)胞用 Dorsomorphin (5-25 μM) 處理 24 h，使用 Flow Cytometry 檢測(cè)細(xì)胞凋亡情況。
結(jié)果：Dorsomorphin 以劑量依賴的方式增加了急性和慢性型 ATL 患者 PBMC 中早期凋亡細(xì)胞的頻率。[2] |
| 體內(nèi)活性 | 方法：為檢測(cè)體內(nèi)抗腫瘤活性，將 Dorsomorphin (10 mg/kg) 腹腔注射給攜帶人類腫瘤 S1T 的 NOD/SCID 小鼠，每天一次，持續(xù)二十八天。
結(jié)果：Dorsomorphin 抑制了 NOD/SCID 小鼠中人 ATL 腫瘤異種移植物的生長(zhǎng)。[2]
方法：為檢測(cè)體內(nèi)對(duì) SMAD 活性的影響，將 Dorsomorphin (10 mg/kg) 單次腹腔注射給 iron-dextran 處理的 C57BL/6 小鼠。
結(jié)果：Dorsomorphin 消除了 iron-dextran 引起的鐵介導(dǎo)的肝臟 SMAD1/5/8 磷酸化的增加。[3] |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | 10% DMSO+90% Saline : 0.13 mg/mL (0.33 mM), Working solution is recommended to be prepared and used immediately.
DMSO : 1.33 mg/mL (3.34 mM), Sonication and heating are recommended.
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| 關(guān)鍵字 | BML275 | AMP-activated protein kinase | inhibit | ATP-competitive | Inhibitor | Dorsomorphin | BMP | Transforming growth factor beta receptors | Autophagy | AMPK | type | receptors | BML 275 | TGF-β Receptor |
| 相關(guān)產(chǎn)品 | Chitosan oligosaccharide | Oxyresveratrol | Guanidine hydrochloride | Naringin | Taurine | Gefitinib | Xylitol | Hydroxychloroquine | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
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