Bookmark and Share
BioAssay: AID 1484

Quantitative High-Throughput Screen for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid Leukemia: Summary

Core Binding Factor (CBF) abnormalities are associated with 20-25% of all acute myeloid leukemias (AML), of which 5-10% are further sub classified as acute myelomonocytic leukemia with eosinophilia, also known as M4Eo in the FAB classification scheme. This subtype of leukemia is usually associated with chromosome 16 inversion (p13:q22). Chromosome 16 inversion results in formation of the fusion more ..
_
   
 Tested Compounds
 Tested Compounds
All(15)
 
 
Active(15)
 
 
 Tested Substances
 Tested Substances
All(15)
 
 
Active(15)
 
 
 Related BioAssays
 Related BioAssays
AID: 1484
Data Source: NCGC (CBFB002)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2009-01-05
Modify Date: 2011-04-13

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 15
Related Experiments
AIDNameTypeComment
1477qHTS Assay for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid LeukemiaConfirmatorydepositor-specified cross reference: qHTS
504370qHTS Assay for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid Leukemia: ME-1 cellular proliferationConfirmatorydepositor-specified cross reference
504371qHTS Assay for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid Leukemia: ME-1 cellular proliferation, SAR for ProbeConfirmatorydepositor-specified cross reference: SAR for probe: ME-1 cellular proliferation
504373qHTS Assay for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid Leukemia: Zebrafish assay for Hematopoiesis, SAR for ProbeOtherdepositor-specified cross reference: SAR for probe: Zebrafish assay
504374qHTS Assay for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid Leukemia: Hit ValidationConfirmatorydepositor-specified cross reference
504375qHTS Assay for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid Leukemia: Hit Validation with Orthogonal AssayConfirmatorydepositor-specified cross reference
504378qHTS Assay for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid Leukemia: SAR for Probe with Orthogonal AssayConfirmatorydepositor-specified cross reference: SAR for probe: Orthogonal assay
504386qHTS Assay for Compounds Blocking the Interaction Between CBF-beta and RUNX1 for the Treatment of Acute Myeloid Leukemia: SAR for ProbeConfirmatorydepositor-specified cross reference: SAR for probe: Primary assay
Description:
NCGC Assay Overview:

Core Binding Factor (CBF) abnormalities are associated with 20-25% of all acute myeloid leukemias (AML), of which 5-10% are further sub classified as acute myelomonocytic leukemia with eosinophilia, also known as M4Eo in the FAB classification scheme. This subtype of leukemia is usually associated with chromosome 16 inversion (p13:q22). Chromosome 16 inversion results in formation of the fusion oncogene CBFB-MYH11, which encodes the fusion protein CBF-beta-SMMHC. This fusion protein binds to RUNX1 (AML1) with high affinity and dominantly inhibits RUNX1 function preventing definitive hematopoiesis.

It has been hypothesized that the interference of CBF-beta and RUNX1 binding could have therapeutic implications for patients with CBF mediated leukemias. We developed a CBF-beta and RUNX1 binding assay in AlphaScreenTM format and optimized it for high throughput screening to search for inhibitors. The goal of this project is to screen MLPCN's compound collection (MLSMR) for identifying the inhibitors of the interaction between CBF-beta and RUNX1 proteins as research probes. If these probes work well in the animal models, the ultimate goal of this project is to development a new drug treatment for this disease.

This assay can not be used to assess how apparent inhibitors interfere with protein binding, and whether inhibitors specifically bind to either protein. Disruption of this protein-protein interaction, through any mechanism, is the intended target activity.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Production centers Network [MLPCN]

MLPCN Grant: X01MH083259-01
Assay Submitter (PI): Paul Liu
Protocol
Please refer to all AIDs linked to this summary for detailed assay protocols for each assay.
Comment
MLSCN probes are given a score of 100. Molecules in the prior art are given a score of 80. Other, less active molecules in the same chemical series as the probe molecules are given a score of 50. Molecules pending validation are given a score of 10. Inactive analogues from these series are given a score of 0. The present results represent compounds with the largest PubChem score from AID 1477.
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Functional
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML223
PubChem Substance ID (SID) for probe 1: 109967254
PubChem Compound ID (CID) for probe 1: 60859
Probe type for probe 1: Inhibitor
IC50/EC50 (nM) for probe 1: 8600
Target for probe 1: CBFb::RUNX1
Disease relevance for probe 1: Leukemia
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK133444/ (ID: 3026048)
Grant number for probe 1: MH083259-01
NCBI Book chapter title for probe 1: ML223: A Small Molecule Probe With In Vivo Activity Against Acute Myeloid Leukemia Subtype M4Eo
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Activity SummaryNature of interaction of the sample with the protein-protein system.String
2CBFb-RUNX1 Potency*The concentration of sample yielding half-maximal activity.FloatμM

* Activity Concentration.
Additional Information
Grant Number: X01MH083259-01

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