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BioAssay: AID 686923

In vitrocounter assay of key BMP4 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(10)
 
 
Active(8)
 
 
Inactive(2)
 
 
 Tested Substances
 Tested Substances
All(10)
 
 
Active(8)
 
 
Inactive(2)
 
 
AID: 686923
Data Source: Vanderbilt Specialized Chemistry Center (In vitrocounter assay against key known off-targets for BMP4..)
BioAssay Type: Panel
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2013-04-10
Hold-until Date: 2014-04-08
Modify Date: 2014-04-08

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 8
Related Experiments
AIDNameTypeProbeComment
652288Developing potent and selective BMP inhibitors as translational tools to develop future therapiesSummary depositor-specified cross reference
652276Discovery and structure-activity relationship of BMP Inhibitors, Secondary in-citro ALK2 AssayConfirmatory same project related to Summary assay
652282Discovery and structure-activity relationship of BMP InhibitorsConfirmatory1 same project related to Summary assay
652284Discovery and structure-activity relationship of BMP Inhibitors, in-vivo SAR, zebrafish embryo 24-well plateOther same project related to Summary assay
686924ML347 Eurofin Panel Assay for BMP Inhibitor (Probe Compound)Other same 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. Here, the Assessment of specific perturbations in embryonic dorsoventral patterning without additional toxicity or nonspecific defects is performed.

Panel Information
BMP_Panel_Assay_TIDs
    Data Table(Active)    Data Table(All)Show more
PID§NameSubstancePanel TargetsDescription
ActiveInactive
1In vitro counter assay against key known off-targets for selectedBMP Compounds73activin receptor-like kinase 1, or ALK1. [gi:116734712]
In vitro kinase assay
2In vitro counter assay against key known off-targets for selectedBMP Compounds91Activin receptor-like kinase 3 or ALK3 [gi:41349437]
In vitro kinase assay
3In vitro counter assay against key known off-targets for selectedBMP Compounds73Activin receptor type-1B or ALK4 [gi:26252117]
In vitro kinase assay
4In vitro counter assay against key known off-targets for selectedBMP Compounds64Transforming growth factor, beta receptor I or ALK5 [gi:47937325]
In vitro kinase assay
5In vitro counter assay against key known off-targets for selectedBMP Compounds91Bone morphogenetic protein receptor type IB (BMPR-IB) [gi:28838626]
In vitro kinase assay
6In vitro counter assay against key known off-targets for selectedBMP Compounds825' AMP-activated protein kinase [gi:19923359]
In vitro kinase assay
7In vitro counter assay against key known off-targets for selectedBMP Compounds73Vascular endothelial growth factor receptor 2 [gi:11321597]
In vitro kinase assay

§ Panel component ID.
Protocol
Inhibition of in vitro kinase activity of purified ALK4, ALK5, TGFR2, ACVR2A, ACVR2B, VEGFR2, PDGFR and AMPK on target peptides in the presence of various concentrations (0.1 to 30 ) of the probe compound.





Positive criterion will be <50% inhibition of ALK4, ALK5, TGFbR2, ACVR2A, ACVR2B, VEGFR2, PDGFbR and AMPK at 10mM (EC > 10mM for each of the 8 kinases). Negative criterion will be >50% inhibition of kinase activity at 10mM (EC > 10mM for each of the 8 kinases). This assay will identify probe compound with increased selectivity for ALK2.












Categorized Comment - additional comments and annotations
From PubChem:
Assay Test Type: In vitro
Result Definitions
Show more
TIDNameDescriptionPID§Panel TargetsHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1ALK1_IC50_uM% Inhibition1activin receptor-like kinase 1, or ALK1.FloatμM
2ALK1_OutcomeActive/Inactive1Outcome
3ALK3_IC50_uM% Inhibition2Activin receptor-like kinase 3 or ALK3FloatμM
4ALK3_OutcomeActive/Inactive2Outcome
5ALK4_IC50_uM% Inhibition3Activin receptor type-1B or ALK4FloatμM
6ALK4_OutcomeActive/Inactive3Outcome
7 ALK5_IC50_uM% Inhibition4Transforming growth factor, beta receptor I or ALK5FloatμM
8ALK5_OutcomeActive/Inactive4Outcome
9ALK6_IC50_uM% Inhibition5Bone morphogenetic protein receptor type IB (BMPR-IB)FloatμM
10ALK6_OutcomeActive/Inactive5Outcome
11AMPK_IC50_uM% Inhibition65' AMP-activated protein kinaseFloatμM
12AMPK_OutcomeActive/Inactive6Outcome
13KDR_IC50_uM% Inhibition7Vascular endothelial growth factor receptor 2FloatμM
14KDR_OutcomeActive/Inactive7Outcome
Additional Information
Grant Number: R01HL104040-02

Classification
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