acalabrutinib   Click here for help

GtoPdb Ligand ID: 8912

Synonyms: ACP-196 | Calquence® | Example 6 [US20140155385 A1] [2]
Approved drug PDB Ligand Immunopharmacology Ligand
acalabrutinib is an approved drug (FDA (2017), EMA (2020))
Compound class: Synthetic organic
Comment: Acalabrutinib is an orally available second-generation, selective and irreversible inhibitor of Bruton tyrosine kinase (BTK) [6], being investigated for its potential antineoplastic activity (in multiple haematologic malignancies and solid tumours), as well as a potential therapy for rheumatoid arthritis. Acalabrutinib covalently bonds to Cysteine-481 in BTK.
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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 8
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 118.51
Molecular weight 465.19
XLogP 4.09
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 CC#CC(=O)N1CCCC1c1nc(c2n1ccnc2N)c1ccc(cc1)C(=O)Nc1ccccn1
Isomeric SMILES CC#CC(=O)N1CCC[C@H]1c1nc(c2n1ccnc2N)c1ccc(cc1)C(=O)Nc1ccccn1
InChI InChI=1S/C26H23N7O2/c1-2-6-21(34)32-15-5-7-19(32)25-31-22(23-24(27)29-14-16-33(23)25)17-9-11-18(12-10-17)26(35)30-20-8-3-4-13-28-20/h3-4,8-14,16,19H,5,7,15H2,1H3,(H2,27,29)(H,28,30,35)/t19-/m0/s1
InChI Key WDENQIQQYWYTPO-IBGZPJMESA-N
Bioactivity Comments
Acalabrutinib has improved selectivity, pharmacologic features (rapid oral absorption, favourable plasma exposure and a short half-life for example) and in vivo target coverage compared to the first generation BTK inhibitor, ibrutinib [3,6]. The IC50 values in the table below are for kinases that contain a cysteine residue aligning with Cysteine-481 in BTK (with exception of LYN). Unlike ibrutinib, acalabrutinib is devoid of activity across the SRC family kinases (IC50s > 1000 nM) [3].
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 Primary target of this compound Hs Inhibitor Inhibition >8.0 pEC50 - 2
⤷ pEC50 >8.0 (EC50 <1x10-8 M) [2]
FYN proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition <6.0 pEC50 - 2
⤷ pEC50 <6.0 (EC50 >1x10-6 M) [2]
LCK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition <6.0 pEC50 - 2
⤷ pEC50 <6.0 (EC50 >1x10-6 M) [2]
LYN proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.0 pEC50 - 2
⤷ pEC50 6.0 (EC50 1x10-6 M) [2]
SRC proto-oncogene, non-receptor tyrosine kinase Hs Inhibitor Inhibition <6.0 pEC50 - 2
⤷ pEC50 <6.0 (EC50 >1x10-6 M) [2]
Bruton tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 8.3 pIC50 - 3
⤷ pIC50 8.3 (IC50 5.1x10-9 M) [3]
BMX non-receptor tyrosine kinase Hs Inhibitor Inhibition 7.3 pIC50 - 3
⤷ pIC50 7.3 (IC50 4.6x10-8 M) [3]
tec protein tyrosine kinase Hs Inhibitor Inhibition 7.0 pIC50 - 3
⤷ pIC50 7.0 (IC50 9.3x10-8 M) [3]
TXK tyrosine kinase Hs Inhibitor Inhibition 6.4 pIC50 - 3
⤷ pIC50 6.4 (IC50 3.68x10-7 M) [3]
BLK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition <6.0 pIC50 - 3
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [3]
IL2 inducible T cell kinase Hs Inhibitor Inhibition <6.0 pIC50 - 3
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [3]
Janus kinase 3 Hs Inhibitor Inhibition <6.0 pIC50 - 3
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [3]
LYN proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition <6.0 pIC50 - 3
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [3]
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
erb-b2 receptor tyrosine kinase 4 Hs Inhibitor Inhibition 7.8 pIC50 - 3
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [3]
epidermal growth factor receptor Hs Inhibitor Inhibition <6.0 pIC50 - 3
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [3]
erb-b2 receptor tyrosine kinase 2 Hs Inhibitor Inhibition <6.0 pIC50 - 3
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [3]