BML-275 (Dorsomorphin)
| MDL | MFCD08705402 |
| 别名 | Dorsomorphin |
| CAS | 866405-64-3 |
| 分子式 | C24H25N5O |
| 分子量 | 399.49 |
| 纯度 | ≥98% |
| 单位 | 瓶 |
| SMILES | C12=C(C3=CC=NC=C3)C=NN1C=C(C4=CC=C(OCCN5CCCCC5)C=C4)C=N2 |
| 靶点 | AMPK |
| 规格 | 10mg 50mg |
Dorsomorphin dihydrochlorideCAS号： 1219168-18-9分子式： C24H27Cl2N5O分子量： 472.41描述纯度储存/保存方法别名外观可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)
| 产品描述 | |
| 描述 |
Dorsomorphin 2HCl(Compound C; BML-275) has been shown to act as a potent and selective inhibitor of AMPK (AMP-activated protein kinase; Ki = 109 nM), induced by AICAR and metformin; also inhibits ALK2, ALK3, and ALK 6 . |
| 纯度 |
>98%
|
| 储存/保存方法 |
Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.
|
| 基本信息 | |
| 别名 |
Dorsomorphin dihydrochloride；Compound C dihydrochloride；BML-275 dihydrochloride
|
| 外观 |
Light yellow powder
|
| 可溶性/溶解性 |
DMSO : 5 mg/mL (10.58 mM; Need ultrasonic)
Water ：50 mg/mL (105.84 mM; Need ultrasonic) |
| 生物活性 | |
| 靶点 |
AMPK；ALK2；ALK3 ；ALK6；Autophagy
|
| In vitro(体外研究) |
Dorsomorphin (compound C) (0-10 μM, 18 h) suppresses 2DG-induced GRP78 promoter activity in human fibrosarcoma HT1080 cells in a dose-dependent manner but has little effect on tunicamycin-induced GRP78 promoter activity. Dorsomorphin (compound C) C also suppresses GRP78 promoter activity induced by glucose withdrawal. Dorsomorphin (compound C) has no effect on 2DG-induced PERK activation and reduces the both basal and 2DG-induced AMPK phosphorylation levels in HT1080 cells.
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| In vivo(体内研究) |
Dorsomorphin (compound C: 10 mg/kg, intravenously once) treatment leads to a 60% increase in total serum iron concentrations, reduces basal levels of hepcidin expression and increasing serum iron concentrations in adult mice.
Dorsomorphin (compound C: 0.2 mg/kg, i.v., 30 min before LPS injection) reduces ICAM-1 and VCAM-1 expression in LPS-injected rat aorta. Dorsomorphin (compound C; 25 mg/kg; i.p. injection, in male BALB/c mice) treatment before lipopolysaccharide (LPS) injection significantly reduces lethality in contrast to animals treated with LPS challenge only. |
分子结构图
Dorsomorphin dihydrochloride
| MDL | MFCD11112197 |
| 别名 | FD5027;Dorsomorphin 2HCl;BML-275;BML-275 2HCl |
| CAS | 1219168-18-9 |
| 分子式 | C24H25N5O·2HCl |
| 分子量 | 472.41 |
| 纯度 | ≥98% |
| 单位 | 支 |
| 生物活性 | Dorsomorphin dihydrochloride是一种有效，选择性和 ATP 竞争性的 AMPK 抑制剂，Ki 为109±16 nM。[1-4] |
| In Vitro | 在2DG应力下, 用10μMDorsomorphin处理HT1080细胞2小时。免疫印迹分析显示, 通过将HT1080细胞暴露于2DG, AMPK的催化α亚基的磷酸化水平增加, 而当添加Dorsomorphin时, 基础和2DG诱导的磷酸化水平明显降低。使用基于ELISA的测定系统测量细胞激酶活性证实, 无论细胞培养条件如何, Dorsomorphin都会降低内源性AMPK活性[2]。 |
| In Vivo | 在24小时内施用Dorsomorphin导致总血清铁浓度增加60％。因此, Dorsomorphin治疗可有效降低成人小鼠铁调素表达的基础水平并增加血清铁浓度[3]。 |
| 激酶实验 | 将HT1080细胞接种在24孔板 (每孔2×10 4个细胞) 中, 并在存在或不存在葡萄糖或10mM 2DG的情况下用Dorsomorphin处理2小时。通过在6孔板中转染质粒DNA (pAMPKα1-wt, pAMPKα1-D168A和pcFlag作为对照) , 在24孔板中接种并用UPR抑制剂处理来制备过表达野生型和显性失活AMPKα1的HT1080细胞。用细胞裂解缓冲液 (20mM Tris-HCl, pH 7.5, 250mM NaCl, 10％甘油, 0.5％NP-40, 1mM EDTA, 1mM EGTA, 0.2mM PMSF, 1μg/ mL胃蛋白酶抑制剂, 0.5) 裂解细胞。 μg/ mL亮抑酶肽, 5mM NaF, 2mM Na 3 Vo4, 2mMβ-甘油磷酸盐, 1mM DTT) 。使用CycLex AMPK激酶测定试剂盒[2]测定对照样品 (在正常生长条件下的载体或pcFlag) 的相对AMPK激酶活性 (重复测定的平均值±SD) 。 |
| SMILES | [H]Cl.[H]Cl.C12=C(C3=CC=NC=C3)C=NN1C=C(C4=CC=C(OCCN5CCCCC5)C=C4)C=N2 |
| 靶点 | AMPK |
| 动物实验 | 小鼠[3]在标准饮食中饲养的12周龄C57BL / 6小鼠通过尾静脉注射0.2g / kg葡聚糖或0.2g / kg铁 – 葡聚糖USP。葡聚糖仅注射载体, 而铁 – 葡聚糖注射载体或Dorsomorphin (10mg / kg) 。注射后1小时, 杀死小鼠并将肝脏片段收集在500μLSDS-裂解缓冲液中并机械均化。通过SDS-PAGE分离20μL肝脏提取物并进行免疫印迹。使用来自机械均质化的小鼠肝脏的Trizol收获总RNA (注射后6小时, 单次腹膜内剂量的Dorsomorphin (10mg / kg) 或DMSO) 。 |
| 细胞实验 | 在存在或不存在10mM 2DG或1μg/ mL衣霉素作为应激源的情况下, 用不同浓度的Dorsomorphin (0, 0.3, 1, 3, 10μM) , Versipelostatin和苯乙双胍处理HeLa和786-O细胞。 h在96孔板中。对于组合研究, 在存在或不存在10mM 2DG的情况下, 用各种浓度的UPR抑制剂处理786-O细胞24小时。然后用新鲜生长培养基替换培养基, 并将细胞再培养15小时。随后, 将MTT添加到培养基中, 并确定每个孔的吸光度。对于在葡萄糖戒断条件下的活力测定, 在存在或不存在葡萄糖的情况下, 在12孔板中用不同浓度的Dorsomorphin和苯乙双胍处理HT1080细胞18小时, 接种在96孔板中的生长培养基中, 然后培养。再添加MTT前48小时。通过将来自未处理细胞的每个对照吸光度设定为100％来计算相对细胞存活率 (一式四份测定的平均值±SD) 。使用等效线法[2]分析药物组合在产生80％细胞生长抑制 (IC80) 的浓度下的作用。 |
| 数据来源文献 | [1]. Zhou G, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct; 108 (8) :1167-74.
[2]. Saito S, et al. Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling. PLoS One. 2012; 7 (9) :e45845. [3]. Yu PB, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008 Jan; 4 (1) :33-41. [4]. Zhang DY, et al. Role of autophagy and its molecular mechanisms in mice intestinal tract after severe burn. J Trauma Acute Care Surg. 2017 Oct; 83 (4) :716-724 |
| 备注 | 以上数据均来自公开文献, Jinpan暂未进行独立验证, 仅供参考。These protocols are for reference only. Jinpan does not independently validate these methods. |
| 规格 | 5mg 10mM *1mL in Water |
是一种有效，选择性和 ATP 竞争性的 AMPK 抑制剂。
Dorsomorphin free baseCAS号： 866405-64-3分子式： C24H25N5O分子量： 399.49描述纯度储存/保存方法别名外观可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)
| 产品描述 | |
| 描述 |
Dorsomorphin(Compound C; BML-275) has been shown to act as a potent and selective inhibitor of AMPK (AMP-activated protein kinase; Ki = 109 nM), induced by AICAR and metformin; also inhibits the bone morphogenetic protein type 1 receptors ACTR-I (ALK2), B |
| 纯度 |
>98%
|
| 储存/保存方法 |
Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.
|
| 基本信息 | |
| 别名 |
BML-275; Compound C; BML275; BML 275
|
| 外观 |
white to beige Powder
|
| 可溶性/溶解性 |
DMSO : 3 mg/mL (7.5 mM), warmed
Ethanol : 2 mg/mL (5.0 mM), warmed |
| 生物活性 | |
| 靶点 |
AMPK
|
| In vitro(体外研究) |
Dorsomorphin inhibits ACC inactivation by either AICAR or metformin, and also attenuates AICAR and metformin’s effect to increase fatty acid oxidation or suppress lipogenic genes in hepatocytes. Inhibition of AMPK activity by Dorsomorphin almost completely inhibits autophagic proteolysis in HT-29 cells. in addition, Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6, and thus blocks BMP-mediated SMAD1/5/8 phosphorylation, target gene transcription and osteogenic differentiation.
|
| In vivo(体内研究) |
Dorsomorphin (10 mg/kg) reduces basal levels of hepcidin expression and increases serum iron concentrations in adult mice. Dorsomorphin (0.2 mg/kg, i.v.) significantly reduces VCAM-1 and ICAM-1 expression in the thoracic aorta of LPS-treated rats.
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分子结构图
