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BioAssay: AID 515832

Inhibition of BCR-ABL1 autophosphorylation in human K562 cells

Although orphan drug applications required by the EMEA must include assessments of similarity to pre-existing products, these can be difficult to quantify. Here we illustrate a paradigm in comparing nilotinib to the prototype kinase inhibitor imatinib, and equate the degree of structural similarity to differences in properties. Nilotinib was discovered following re-engineering of imatinib, more ..
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 Tested Compounds
 Tested Compounds
All(2)
 
 
Active(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Active(2)
 
 
AID: 515832
Data Source: ChEMBL (663686)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-09-17
Modify Date: 2015-04-12

Data Table ( Complete ):           View Active Data    View All Data
Targets
Sequence: RecName: Full=Tyrosine-protein kinase ABL1; AltName: Full=Abelson murine leukemia viral oncogene homolog 1; AltName: Full=Abelson tyrosine-protein kinase 1; AltName: Full=Proto-oncogene c-Abl; AltName: Full=p150
Description ..   
Protein Family: Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase
Comment ..   

Gene:ABL1     Related Protein 3D Structures     More BioActivity Data..


more...  
BioActive Compounds: 2
Description:
Title: Structural resemblances and comparisons of the relative pharmacological properties of imatinib and nilotinib.

Abstract: Although orphan drug applications required by the EMEA must include assessments of similarity to pre-existing products, these can be difficult to quantify. Here we illustrate a paradigm in comparing nilotinib to the prototype kinase inhibitor imatinib, and equate the degree of structural similarity to differences in properties. Nilotinib was discovered following re-engineering of imatinib, employing structural biology and medicinal chemistry strategies to optimise cellular potency and selectivity towards BCR-ABL1. Through evolving only to conserve these properties, this resulted in significant structural differences between nilotinib and imatinib, quantified by a Daylight-fingerprint-Tanimoto similarity coefficient of 0.6, with the meaning of this absolute measure being supported by an analysis of similarity distributions of similar drug-like molecules. This dissimilarity is reflected in the drugs having substantially different preclinical pharmacology and a lack of cross-intolerance in CML patients, which translates into nilotinib being an efficacious treatment for CML, with a favourable side-effect profile.
(PMID: 20817538)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type:
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Cell Type: K562
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatnM
6IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

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