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BioAssay: AID 652282

Discovery and structure-activity relationship of BMP Inhibitors

Because the heart has negligible intrinsic capacity to regenerate new tissues to replace those lost to injury, there is currently no definitive heart failure treatment, other than organ transplantation. Recent studies have introduced the prospect of replacing damaged heart tissues with healthy cardiomyocytes derived from pluripotent stem cells. However, realizing the full therapeutic potential of more ..
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 Tested Compounds
 Tested Compounds
All(17)
 
 
Probe(1)
 
 
Active(16)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(17)
 
 
Probe(1)
 
 
Active(16)
 
 
Inactive(1)
 
 
AID: 652282
Data Source: Vanderbilt Specialized Chemistry Center (Cell-Based BMP Reporter Assay)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2013-04-04
Hold-until Date: 2014-04-04
Modify Date: 2014-04-07

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: Bone morphogenetic protein 4 [Homo sapiens]
Description ..   
Protein Family: TGF-beta propeptide

Gene:BMP4     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: Chemical Probe: 1    Active: 16
Related Experiments
AIDNameTypeComment
652288Developing potent and selective BMP inhibitors as translational tools to develop future therapiesSummarydepositor-specified cross reference
652276Discovery and structure-activity relationship of BMP Inhibitors, Secondary in-citro ALK2 AssayConfirmatorysame project related to Summary assay
652284Discovery and structure-activity relationship of BMP Inhibitors, in-vivo SAR, zebrafish embryo 24-well plateOthersame project related to Summary assay
686923In vitrocounter assay of key BMP4 InhibitorsOthersame project related to Summary assay
686924ML347 Eurofin Panel Assay for BMP Inhibitor (Probe Compound)Othersame project related to Summary assay
Description:
Assay Provider: Charles Hong

Assay Provider Affiliation: Vanderbilt University

Because the heart has negligible intrinsic capacity to regenerate new tissues to replace those lost to injury, there is currently no definitive heart failure treatment, other than organ transplantation. Recent studies have introduced the prospect of replacing damaged heart tissues with healthy cardiomyocytes derived from pluripotent stem cells. However, realizing the full therapeutic potential of stem cells faces numerous hurdles, including the potential for tumor formation, a low rate of cardiomyocyte formation, and an inadequate mechanistic understanding of cardiomyogenesis. Additionally, translational efforts are hampered by a lack of pharmaceutical agents to boost therapeutic effects of stem cells. Dorsomorphin, the first known small molecule inhibitor of the bone morphogenetic protein (BMP) signaling, is one of the most potent chemical inducers of cardiomyogenesis in mouse embryonic stem (ES) cells. Dorsomorphin treatment during the initial 24 to 48 hours of ES cell differentiation was sufficient for robust cardiomyocyte induction. Strikingly, the massive cardiac induction occurs apparently in the absence of mesoderm induction and at the expense of other mesoderm-derived lineages, including endothelial, smooth muscle and hematopoietic lineages. From these results, we hypothesize that atimely BMP signal inhibition commits the primitive multipotent progenitor cells toward the cardiomyocyte development. The aim is to develop potent and selective BMP inhibitors with excellent pharmaceutical properties (no cellular toxicity, high solubility, limited off-target activity) for use in directed differentiation of pluripotent stem cell toward cardiac development



Protocol
C2C12BRA BMP reporter cells will be stimulated with BMP4 in the presence of various concentrations of the probe compounds. After 24-hours, cells will be lysed, and the Luciferase activities measured using the SteadyGlo Lucifease Assay reagents (Promega), and cell titers measured using the Cell Titer Glo (Promega)
Positive criterion is BRE-Luciferase activity less than 50% of DMSO controls at 1uM (IC50 < 1mM). Negative criterion is BRE-Luciferase activity greater than 50% of DMSO controls at 1uM.
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1IC50_uM*IC50FloatμM
2CategoryHow the compound is classified as, Inhibitor or InactiveString
3Value_at_0.0_uM_1 (0μM**)See ProtocolFloat
4Value_at_0.1_uM_1 (0.1μM**)See ProtocolFloat
5Value_at_0.5_uM_1 (0.5μM**)See ProtocolFloat
6Value_at_1.0_uM_1 (1μM**)See ProtocolFloat
7Value_at_5_uM_1 (5μM**)See ProtocolFloat
8Value_at_10_uM_1 (10μM**)See ProtocolFloat

* Activity Concentration. ** Test Concentration.
Additional Information
Grant Number: R01HL104040-02

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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