BIIB068   Click here for help

GtoPdb Ligand ID: 11178

Synonyms: BIIB-068 | compound 1 [PMID: 32696648]
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: BIIB068 was designed as a novel, oral Bruton's tyrosine kinase (BTK) inhibitor and is intended for the treatment of autoimmune diseases [1]. Pharmacokinetics of BIIB068 in humans have been determined in a Phase 1 study following a single, ascending oral dose.
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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

BIIB068 is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 9
Topological polar surface area 97.2
Molecular weight 435.24
XLogP 2.73
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC(OC1CN(C1)C(=O)NCc1ccc(cc1C)c1ccnc(n1)Nc1cnn(c1)C)C
Isomeric SMILES CC(OC1CN(C1)C(=O)NCc1ccc(cc1C)c1ccnc(n1)Nc1cnn(c1)C)C
InChI InChI=1S/C23H29N7O2/c1-15(2)32-20-13-30(14-20)23(31)25-10-18-6-5-17(9-16(18)3)21-7-8-24-22(28-21)27-19-11-26-29(4)12-19/h5-9,11-12,15,20H,10,13-14H2,1-4H3,(H,25,31)(H,24,27,28)
InChI Key BMWMKGNVAMXXCH-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
BIIB068 dose-dependently inhibits BTK phosphorylation and B-cell activation, although inhibition of B-cell activation was not observed to be as robust as expected based on the level of pBTK inhibition [1]. In a DiscoverX kinome screen, BIIB068 exhibited >400-fold selectivity for BTK compared to the other kinases tested, including the structurally related Tec family kinases (BMX, ITK, TEC, TXK).
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 9.5 pKd - 1
⤷ pKd 9.5 (Kd 3x10-10 M) [1]
mitogen-activated protein kinase kinase kinase 19 Hs Inhibitor Inhibition 6.9 pKd - 1
⤷ pKd 6.9 (Kd 1.3x10-7 M) [1]
Janus kinase 2 Hs Inhibitor Inhibition 6.3 pKd - 1
⤷ pKd 6.3 (Kd 4.6x10-7 M) [1]
Bruton tyrosine kinase Hs Inhibitor Inhibition 9.0 pIC50 - 1
⤷ pIC50 9.0 (IC50 1x10-9 M) [1]
Description: Biochemical assay measuring enzyme activity inhibition.