orelabrutinib   Click here for help

GtoPdb Ligand ID: 10629

Synonyms: example 3 [WO2015048662A2] | ICP-022 | ICP022
Approved drug Immunopharmacology Ligand
orelabrutinib is an approved drug (China (2020))
Compound class: Synthetic organic
Comment: The chemical structure that was submitted to the WHO for the INN orelabrutinib, is identical to the structure of example 3 that is claimed as a BTK inhibitor in patent WO2015048662A2 [2]. The inhibitors in WO2015048662A2 are claimed for their potential to treat cancers [1] and inflammatory/autoimmune diseases that are mediated, at least in part, by Bruton's tyrosine kinase (BTK). Innocare Pharma have declared the ICP-022>orelabrutinib association on their company news webpage. Orelabrutinib is an orally administered, potent, irreversible and selective BTK-inhibitor.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 85.52
Molecular weight 427.19
XLogP 3.62
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)N1CCC(CC1)c1ccc(c(n1)c1ccc(cc1)Oc1ccccc1)C(=O)N
Isomeric SMILES C=CC(=O)N1CCC(CC1)c1ccc(c(n1)c1ccc(cc1)Oc1ccccc1)C(=O)N
InChI InChI=1S/C26H25N3O3/c1-2-24(30)29-16-14-18(15-17-29)23-13-12-22(26(27)31)25(28-23)19-8-10-21(11-9-19)32-20-6-4-3-5-7-20/h2-13,18H,1,14-17H2,(H2,27,31)
InChI Key MZPVEMOYADUARK-UHFFFAOYSA-N
Bioactivity Comments
1 μM of ICP-022 inhibits BTK kinase activity by >99% in vitro [2]. In comparison Src activity is inhibited by only 23% at this concentration of ICP-022. Percentage inhibition of other Src family kinase (% in brackets) were: BLK (51), LCK (11), LYN (3), YES (8), FGR, FYN and HCK (no inhibition detected).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Bruton tyrosine kinase Hs Inhibitor Inhibition 8.4 pIC50 - 2
⤷ pIC50 8.4 (IC50 4.4x10-9 M) [2]
Description: Biochemical inhibition determined using a proprietary ADP-Glo kinase assay.