EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73632_C
Activin/Nodal/TGFβ 通路抑制剂；抑制 ALK2
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总览
DMH1（dorsomorphin homolog 1）是激活素受体样激酶2（ALK2；IC₅₀=13-108 nM）的选择性抑制剂，ALK2是 I 型骨形态发生蛋白（BMP）受体（Hao et al.; Mohedas et al.）。DMH1对ALK4、ALK5、AMPK、KDR（VEGFR2）或PDGFRβ没有可检测到的抑制作用，尽管它在nM浓度下抑制ALK1和ALK3（Hao et al.; Mohedas et al.）。
分化
·诱导小鼠胚胎干细胞分化为心肌细胞祖细胞（Ao et al.）。
·诱导人诱导多能干细胞分化为表达SOX1和PAX6的神经前体细胞（Neely et al.）。
·在斑马鱼早期胚胎中，使胚胎轴背侧化，但不破坏血管生成过程（Hao et al. 2010）。
癌症研究
·抑制非小细胞肺癌细胞体外生长、迁移和侵袭，并减弱体内异种移植肺肿瘤的生长（Hao et al. 2014）。
·抑制化疗药物诱导的自噬反应（Sheng et al.）。
细胞类型
癌细胞及细胞系，心肌细胞，PSC衍生，神经细胞，PSC衍生，神经干/祖细胞，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
癌症，干细胞生物学
CAS 编号
1206711-16-1
化学式
C₂₄H₂₀N₄O
纯度
≥98%
通路
Activin/Nodal/TGFβ
靶点
ALK2
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应用领域
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相关材料与文献
技术资料 (5)
文献 (7)
In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors.
ACS chemical biology 2010 FEB
Abstract
The therapeutic potential of small molecule signaling inhibitors is often limited by off-target effects. Recently,in a screen for compounds that perturb the zebrafish embryonic dorsoventral axis,we identified dorsomorphin,the first selective inhibitor of bone morphogenetic protein (BMP) signaling. Here we show that dorsomorphin has significant off-target" effects against the VEGF (vascular endothelial growth factor) type-2 receptor (Flk1/KDR) and disrupts zebrafish angiogenesis. Since both BMP and VEGF signals are known to be involved in vascular development�
Chemical 'Jekyll and Hyde's: small-molecule inhibitors of developmental signaling pathways.
Chemical Society reviews 2011 AUG
Abstract
Small molecules that perturb developmental signaling pathways can have devastating effects on embryonic patterning,as evidenced by the chemically induced onset of cyclopic lambs and children with severely shortened limbs during the 1950s. Recent studies,however,have revealed critical roles for these pathways in human disorders and diseases,spurring the re-examination of these compounds as new targeted therapies. In this tutorial review,we describe four case studies of teratogenic compounds,including inhibitors of the Hedgehog (Hh),Wnt,and bone morphogenetic protein (BMP) pathways. We discuss how these teratogens were discovered,their mechanisms of action,their utility as molecular probes,and their potential as therapeutic agents. We also consider current challenges in the field and possible directions for future research.
DMH1, a novel BMP small molecule inhibitor, increases cardiomyocyte progenitors and promotes cardiac differentiation in mouse embryonic stem cells.
PloS one 2012 JAN
Abstract
The possibility of using cell-based therapeutics to treat cardiac failure has generated significant interest since the initial introduction of stem cell-based technologies. However,the methods to quickly and robustly direct stem cell differentiation towards cardiac cell types have been limited by a reliance on recombinant growth factors to provide necessary biological cues. We report here the use of dorsomorphin homologue 1 (DMH1),a second-generation small molecule BMP inhibitor based on dorsomorphin,to efficiently induce beating cardiomyocyte formation in mouse embryonic stem cells (ESCs) and to specifically upregulate canonical transcriptional markers associated with cardiac development. DMH1 differs significantly from its predecessor by its ability to enrich for pro-cardiac progenitor cells that respond to late-stage Wnt inhibition using XAV939 and produce secondary beating cardiomyocytes. Our study demonstrates the utility of small molecules to complement existing in vitro cardiac differentiation protocols and highlights the role of transient BMP inhibition in cardiomyogenesis.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 1206711-16-1 |
| Chemical Formula | C₂₄H₂₀N₄O |
| 纯度 | ≥ 98% |
| Target | ALK2 |
| Pathway | Activin/Nodal/TGFβ |
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