Inhibition of autophosphorylation of DDR2 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 ..
BioActive Compounds: 2
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.
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
ChEMBL Target ID: 101079
Target Type: SINGLE PROTEIN
Pref Name: Discoidin domain-containing receptor 2
Synonyms: CD167 antigen-like family member B;CD_antigen=CD167b;Discoidin domain receptor 2;Discoidin domain-containing receptor 2;Discoidin domain-containing receptor tyrosine kinase 2;Neurotrophic tyrosine kinase; receptor-related 3;Receptor protein-tyrosine kinase TKT;Tyrosine-protein kinase TYRO10;
Gene Name: DDR2;NTRKR3 ;TKT;TYRO10;
Protein Accession: Q16832;
Protein GI: 215273969;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: enzyme kinase protein kinase tyr tk ddr ddr
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Assay Cell Type: HEK293
* Activity Concentration.
Data Table (Concise)