Clare K. Murphy's research while affiliated with Vanderbilt University and other places

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Publications (9)

Schemes for Synthesis of Windorphen and BAS, Related to Experimental...
WD Blocks Wnt Signaling Downstream of β-Catenin Destruction Complex
WD, which Dorsalizes Zebrafish Embryo, Inhibits Canonical Wnt Signaling
Windorphen Does Not Disrupt Its Interaction of β-Catenin with Its...
+5 Multispecies Sequence Comparison of C-Terminal Transactivation Domains...
Selective Small Molecule Targeting β-Catenin Function Discovered by In Vivo Chemical Genetic Screen
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  • Sep 2013
The canonical Wnt signaling pathway, mediated by the transcription factor β-catenin, plays critical roles in embryonic development and represents an important therapeutic target. In a zebrafish-based in vivo screen for small molecules that specifically perturb embryonic dorsoventral patterning, we discovered a compound named windorphen that selecti...
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Abstract 5426: Identification of Selective Small Molecule Inhibitors of Vascular Endothelial Growth Factor (VEGF) and Bone Morphogenetic Protein (BMP) Signaling Using Zebrafish-based in vivo Structure Activity Relationship Studies
Article
  • Nov 2009
Angiogenesis, a physiological process of forming new blood vessels from pre-existing ones, plays a vital role in organogenesis, tissue response to ischemia, and malignant tumor growth. Angiogenesis is a complex process, requiring a finely tuned balance between various stimulatory and inhibitory signals. Vascular endothelial growth factors (VEGFs) a...
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Movie S1
Data
  • Aug 2008
Spontaneously contracting focus of cardiomyocytes expressing DsRed-Nuc protein under the α-MHC promoter formed from dorsomorphin-treated ES cells at day 12 of differentiation. (1.15 MB AVI)
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Figure S1
Data
  • Aug 2008
Dorsomorphin treatment from day −3 to 2 promotes cardiomyogenesis at the expense of other mesodermal lineages. (A) Dorsomorphin treatment (from day −3 to 2) blunted the induction of BryT expression at day 3 of differentiation (*p = 0.01), but resulted in higher BryT expression at day 4, in comparison to controls (**p = 0.0424). Dorsomorphin treatme...
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Movie S2
Data
  • Aug 2008
Phase contrast movie of spontaneously contracting foci of cardiomyocytes formed from dorsomorphin-treated ES cells on a gelatin-coated plate. (0.89 MB AVI)
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Movie S3
Data
  • Aug 2008
Spontaneously contracting EB formed from dorsomorphin-treated ES cells on a 96-well microtiter plate. (0.81 MB AVI)
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Figure S2
Data
  • Aug 2008
Dorsomorphin (DM) treatment of ES cells efficiently blocks activation of the BMP-target gene Id1. Treatment of mouse ES cells with 2 µM DM from day 0 to 1 of differentiation resulted in a 96.1% reduction in the expression levels of the BMP-target gene Id1 at day 1 (*p<0.0001). All results are compared to DMSO-vehicle treatment as negative control....
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Figure 1. The small molecule BMP inhibitor, dorsomorphin, induces...
Figure 3. Dorsomorphin treatment during the initial 24 hours of ES cell...
Figure 4. Dorsomorphin treatment promotes the formation of large areas...
Figure 5. Dorsomorphin treatment promotes cardiomyogenesis at the...
+4 (A) Chemical structures of dorsomorphin (DM), a selective BMP...
Dorsomorphin, a Selective Small Molecule Inhibitor of BMP Signaling, Promotes Cardiomyogenesis in Embryonic Stem Cells
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  • Feb 2008
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...
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Citations

... To discover new potential regulators of cancer, we turned to developmental processes, as key regulators of embryonic development are known to play critical roles in cancer [27][28][29][30]. We conducted an unbiased chemical genetic screen of ~ 30,000 compounds to identify novel small molecules that selectively perturb zebrafish development [25,26,31,32]. This screening effort led to the identification of 5-ethyl-5'-(1-naphthyl)-3'H-spiro [indole-3,2'-[1, 3, 4]thiadiazole]-2-one, herein named ogremorphin-1 (OGM1) (Fig. 1A). ...
Reference: GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment
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... [33]. Dorsomorphin, as an inhibitor of BMP signaling pathway, can induce Smad activation and promote the generation of cardiomyocytes [34]. The inhibition of HDAC by VPA enables the regulation of cellular proliferation, apoptosis, and differentiation [35]. ...
Reference: Regulation of cardiac fibroblasts reprogramming into cardiomyocyte‐like cells with a cocktail of small molecule compounds
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