Bookmark and Share
BioAssay: AID 515833

Inhibition of autophosphorylation of CSF1R expressed in HEK293 cells by ELISA

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 ..
_
   
 Tested Compounds
 Tested Compounds
All(2)
 
 
Active(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Active(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 515833
Data Source: ChEMBL (663687)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-09-17
Modify Date: 2013-11-17

Data Table ( Complete ):           Active    All
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.

Putative Target:

ChEMBL Target ID: 12840
Target Type: SINGLE PROTEIN
Pref Name: Macrophage colony stimulating factor receptor
Synonyms: CD_antigen=CD115;CSF-1 receptor;CSF-1-R;CSF-1R;M-CSF-R;Macrophage colony-stimulating factor 1 receptor;Proto-oncogene c-Fms;
Gene Name: CSF1R;FMS;
Protein Accession: P07333;
Protein GI: 547770;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: enzyme kinase protein kinase tyr tk pdgfr
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Assay Cell Type: HEK293

Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatnM
10IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
PageFrom: