化合物Dorsomorphin dihydrochloride T6146

Product Introduction
Bioactivity


英文名: Dorsomorphin dihydrochloride

描述: Dorsomorphin dihydrochloride (BML-275 2HCl) 是一种选择性和 ATP 竞争性的AMPK 抑制剂，Ki 为 109 nM。它诱导自噬，通过靶向抑制 I 型受体ALK2，ALK3和ALK6来抑制 BMP 途径。

细胞实验: 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].

激酶实验: 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].

动物实验: 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].

体外活性: Dorsomorphin (compound C) is a potent reversible inhibitor that is competitive with ATP, with Ki = 109 ± 16 nM in the absence of AMP. Incubation of cultured hepatocytes with compound C inhibited ACC inactivation by either AICAR or metformin [1]. Compound C suppressed 2-deoxy-D-glucose (2DG)-induced GRP78 promoter activity in a dose-dependent manner but had little effect on tunicamycin-induced GRP78 promoter activity. Compound C also suppressed GRP78 promoter activity induced by glucose withdrawal [2].

体内活性: 6 h after dorsomorphin was administered intravenously, hepatic hepcidin mRNA levels were reduced to one-third of that of vehicle-injected mice. Alterations in hepcidin levels affect serum iron concentrations within 24 h via the altered mobilization of intracellular iron by ferroportin33. Administration of dorsomorphin over 24 h led to a 60% increase in total serum iron concentrations [3].

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 10 mM
H2O : 47.2 mg/mL (100 mM)


关键字: 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

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相关库: Antioxidant Compound Library | Anti-Aging Compound Library | AMPK-Targeted Compound Library | Oxidation-Reduction Compound Library | Anti-Cancer Compound Library | Anti-Metabolism Disease Compound Library | Inhibitor Library | Kinase Inhibitor Library | TGF-beta/Smad Compound Library | Reprogramming Compound Library

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