| 名稱 | Dorsomorphin dihydrochloride |
| 描述 | Dorsomorphin dihydrochloride (BML-275 2HCl) is an AMPK inhibitor (Ki=109 nM) that is selective and ATP-competitive. Dorsomorphin dihydrochloride inhibits the BMP type I receptors ALK2, ALK3, and ALK6. Dorsomorphin dihydrochloride induces autophagy, and possesses antitumor activity. |
| 細(xì)胞實(shí)驗(yàn) | C2C12 cells were seeded into 96-well plates at 2,000 cells per well in DMEM supplemented with 2% FBS. Wells were treated in quadruplicate with BMP ligands and dorsomorphin or vehicle. Cells were harvested after 5 d in culture with 50 μl Tris-buffered saline, 1% Triton X-100. Lysates were added to p-nitro-phenylphosphate reagent in 96-well plates for 1 h, and alkaline phosphatase activity expressed as absorbance at 405 nM. Cell viability and quantity were measured by Cell-titer Glo and binding of nuclear dye CyQuant, respectively, using replicate wells treated identically to those used for alkaline phosphatase measurements [3]. |
| 激酶實(shí)驗(yàn) | Liver AMPK was partially purified from male SD rats to the blue-Sepharose step. The 100-μl reaction mixture contained 100 μM AMP, 100 μM ATP (0.5 μCi 33P-ATP per reaction), and 50 μM SAMS in a buffer (40 mM HEPES, pH 7.0, 80 mM NaCl, 0.8 mM EDTA, 5 mM MgCl2, 0.025% BSA, and 0.8 mM DTT). The reaction was initiated with the addition of the enzyme. After a 30-minute incubation at 30°C, the reaction was stopped by addition of 80 μl 1% H3PO4. Aliquots (100 μl) were transferred to 96-well MultiScreen plates. The plate was washed three times with 1% H3PO4 followed by detection in a Top-count. The in vitro AMPK inhibition data obtained with compound C — (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine — were fit to the following equation for competitive inhibition by nonlinear regression using a least-squares Marquardt algorithm in a computer program written by N. Thornberry of Merck Research Laboratories: Vi/Vo = (Km + S)/[S + Km × (1 + I/Ki)], where Vi is the inhibited velocity, Vo is the initial velocity, S is the substrate (ATP) concentration, Km is the Michaelis constant for ATP, I is the inhibitor (compound C) concentration, and Ki is the dissociation constant for compound C [1]. |
| 動(dòng)物實(shí)驗(yàn) | 12-week-old C57BL/6 mice raised on a standard diet were injected via the tail vein with 0.2 g kg?1 of dextran (average MW = 5,000) or 0.2 g kg?1 of iron-dextran USP. Dextran was injected with vehicle only, whereas iron-dextran was injected with either vehicle or dorsomorphin (10 mg/kg). 1 h after injection, mice were killed and liver segments were collected in 500 μl of SDS-lysis buffer and mechanically homogenized. 20 μl of liver extracts were resolved by SDS-PAGE and immunoblotted. Total RNA was harvested using Trizol from mechanically homogenized mouse livers (6 h after injection with a single intraperitoneal dose of dorsomorphin (10 mg/kg) or DMSO) [3]. |
| 體外活性 | 方法：人腫瘤細(xì)胞 HeLa 和 HCT116 用 Dorsomorphin dihydrochloride (1.25-80 μM) 處理 24 h，使用 CCK-8 assay 檢測細(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 患者來源的 PBMCs 細(xì)胞用 Dorsomorphin dihydrochloride (5-25 μM) 處理 24 h，使用 Flow Cytometry 檢測細(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：為檢測體內(nèi)抗腫瘤活性，將 Dorsomorphin dihydrochloride (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。[2]
方法：為檢測體內(nèi)對 SMAD 活性的影響，將 Dorsomorphin dihydrochloride (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] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 6.88 mg/mL (14.55 mM), Sonication is recommended.
H2O : 47.2 mg/mL (100 mM)
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| 關(guān)鍵字 | Dorsomorphin (Compound C) | Compound C | BML 275 | BML275 Dihydrochloride | Dorsomorphin | BMP | AMPK | TGF-β Receptor | Compound C Dihydrochloride | Dorsomorphin Dihydrochloride | Dorsomorphin dihydrochloride | inhibit | Autophagy | BML-275 Dihydrochloride | type | ATP-competitive | BML 275 Dihydrochloride | Transforming growth factor beta receptors | receptors | pathway | BML-275 | AMP-activated protein kinase | Inhibitor | BML275 |
| 相關(guān)產(chǎn)品 | Chitosan oligosaccharide | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 抗癌細(xì)胞代謝庫 | 線粒體靶向庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | AMPK靶向分子庫 | TGF-β/Smad靶點(diǎn)化合物庫 | 神經(jīng)元分化化合物庫 |