EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #72102_C
BMP 和 AMPK 通路抑制剂；抑制 ALK2、ALK3、ALK6 和 AMPK
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总览
Dorsomorphin 通过靶向 I 型 BMP 受体激活素受体样激酶 (ALK) 2、ALK3 和 ALK6 来抑制骨形态发生蛋白 (BMP) 通路。它也是 AMP 活化蛋白激酶 (AMPK；Ki = 109 nM) 的强效抑制剂，但对 ZAPK、SYK、PKCθ、PKA 或 JAK3 等结构相关激酶的抑制作用不显著 （Bain et al., Yu et al.）。
分化
·促进人多能干细胞向神经祖细胞分化 （Morizane et al., Zhou et al.）。
·促进小鼠和人多能干细胞向心肌细胞分化（Hao et al., Kattman et al.）。
·促进脂肪细胞分化，抑制人间充质细胞向成骨细胞分化（Kim et al.）。
细胞类型
脂肪细胞，心肌细胞，PSC衍生，间充质干/祖细胞，神经细胞，PSC衍生，多能干细胞
种属
人，小鼠，非人灵长类，其他物种，大鼠
应用
分化
研究领域
神经科学，干细胞生物学
CAS 编号
866405-64-3
化学式
C₂₄H₂₅N₅O
纯度
≥98%
通路
AMPK，BMP
靶点
ALK2，ALK3，ALK6，AMPK
产品说明书及文档
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应用领域
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相关材料与文献
技术资料 (4)
文献 (7)
The selectivity of protein kinase inhibitors: a further update.
The Biochemical journal 2007 DEC
Abstract
The specificities of 65 compounds reported to be relatively specific inhibitors of protein kinases have been profiled against a panel of 70-80 protein kinases. On the basis of this information,the effects of compounds that we have studied in cells and other data in the literature,we recommend the use of the following small-molecule inhibitors: SB 203580/SB202190 and BIRB 0796 to be used in parallel to assess the physiological roles of p38 MAPK (mitogen-activated protein kinase) isoforms,PI-103 and wortmannin to be used in parallel to inhibit phosphatidylinositol (phosphoinositide) 3-kinases,PP1 or PP2 to be used in parallel with Src-I1 (Src inhibitor-1) to inhibit Src family members; PD 184352 or PD 0325901 to inhibit MKK1 (MAPK kinase-1) or MKK1 plus MKK5,Akt-I-1/2 to inhibit the activation of PKB (protein kinase B/Akt),rapamycin to inhibit TORC1 [mTOR (mammalian target of rapamycin)-raptor (regulatory associated protein of mTOR) complex],CT 99021 to inhibit GSK3 (glycogen synthase kinase 3),BI-D1870 and SL0101 or FMK (fluoromethylketone) to be used in parallel to inhibit RSK (ribosomal S6 kinase),D4476 to inhibit CK1 (casein kinase 1),VX680 to inhibit Aurora kinases,and roscovitine as a pan-CDK (cyclin-dependent kinase) inhibitor. We have also identified harmine as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro. The results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes. Despite being used widely,many of the compounds that we analysed were too non-specific for useful conclusions to be made,other than to exclude the involvement of particular protein kinases in cellular processes.
Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism.
Nature chemical biology 2008 JAN
Abstract
Bone morphogenetic protein (BMP) signals coordinate developmental patterning and have essential physiological roles in mature organisms. Here we describe the first known small-molecule inhibitor of BMP signaling-dorsomorphin,which we identified in a screen for compounds that perturb dorsoventral axis formation in zebrafish. We found that 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. Using dorsomorphin,we examined the role of BMP signaling in iron homeostasis. In vitro,dorsomorphin inhibited BMP-,hemojuvelin- and interleukin 6-stimulated expression of the systemic iron regulator hepcidin,which suggests that BMP receptors regulate hepcidin induction by all of these stimuli. In vivo,systemic challenge with iron rapidly induced SMAD1/5/8 phosphorylation and hepcidin expression in the liver,whereas treatment with dorsomorphin blocked SMAD1/5/8 phosphorylation,normalized hepcidin expression and increased serum iron levels. These findings suggest an essential physiological role for hepatic BMP signaling in iron-hepcidin homeostasis.
Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells.
PloS one 2008 JAN
Abstract
BACKGROUND Pluripotent embryonic stem (ES) cells,which have the capacity to give rise to all tissue types in the body,show great promise as a versatile source of cells for regenerative therapy. However,the basic mechanisms of lineage specification of pluripotent stem cells are largely unknown,and generating sufficient quantities of desired cell types remains a formidable challenge. Small molecules,particularly those that modulate key developmental pathways like the bone morphogenetic protein (BMP) signaling cascade,hold promise as tools to study in vitro lineage specification and to direct differentiation of stem cells toward particular cell types. METHODOLOGY/ PRINCIPAL FINDINGS We describe the use of dorsomorphin,a selective small molecule inhibitor of BMP signaling,to induce myocardial differentiation in mouse ES cells. Cardiac induction is very robust,increasing the yield of spontaneously beating cardiomyocytes by at least 20 fold. Dorsomorphin,unlike the endogenous BMP antagonist Noggin,robustly induces cardiomyogenesis when treatment is limited to the initial 24-hours of ES cell differentiation. Quantitative-PCR analyses of differentiating ES cells indicate that pharmacological inhibition of BMP signaling during the early critical stage promotes the development of the cardiomyocyte lineage,but reduces the differentiation of endothelial,smooth muscle,and hematopoietic cells. CONCLUSIONS/ SIGNIFICANCE Administration of a selective small molecule BMP inhibitor during the initial stages of ES cell differentiation substantially promotes the differentiation of primitive pluripotent cells toward the cardiomyocytic lineage,apparently at the expense of other mesodermal lineages. Small molecule modulators of developmental pathways like dorsomorphin could become versatile pharmacological tools for stem cell research and regenerative medicine.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 866405-64-3 |
| Chemical Formula | C₂₄H₂₅N₅O |
| 纯度 | ≥ 98% |
| Target | ALK2, ALK3, ALK6, AMPK |
| Pathway | AMPK, BMP |
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