rilzabrutinib   Click here for help

GtoPdb Ligand ID: 9993

Synonyms: Example 31 [WO2014039899] | PRN-1008 | PRN1008
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Rilzabrutinib (PRN1008) is an oral, reversible covalent inhibitor of Bruton's tyrosine kinase (BTK) [1]. The chemical structure of PRN1008 has not been formally disclosed, and there is some uncertainty of its precise stereochemistry evident in online resources. One possible structure is claimed as Example 31 in Principia Biopharma patent WO2014039899 [2] and this is depicted in PubChem CID 118325989 as the R form without E/Z specification. We show the (E,R) structure here.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 10
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 138.66
Molecular weight 665.32
XLogP 3.67
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES N#CC(=CC(N1CCN(CC1)C1COC1)(C)C)C(=O)N1CCCC(C1)n1nc(c2c1ncnc2N)c1ccc(cc1F)Oc1ccccc1
Isomeric SMILES N#C/C(=C\C(N1CCN(CC1)C1COC1)(C)C)/C(=O)N1CCC[C@H](C1)n1nc(c2c1ncnc2N)c1ccc(cc1F)Oc1ccccc1
InChI InChI=1S/C36H40FN9O3/c1-36(2,45-15-13-43(14-16-45)26-21-48-22-26)18-24(19-38)35(47)44-12-6-7-25(20-44)46-34-31(33(39)40-23-41-34)32(42-46)29-11-10-28(17-30(29)37)49-27-8-4-3-5-9-27/h3-5,8-11,17-18,23,25-26H,6-7,12-16,20-22H2,1-2H3,(H2,39,40,41)/b24-18+/t25-/m1/s1
InChI Key LCFFREMLXLZNHE-GBOLQPHISA-N
Bioactivity Comments
PRN1008's ability to inhibit mouse collagen-induced arthritis was evaluated and reported in the patent application [2].
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 8.8 pIC50 - 2
⤷ pIC50 8.8 (IC50 1.5x10-9 M) [2]
Description: Measured in a caliper-based kinase assay, to assess inhibition of recombinant human BTK kinase activity (@ 16 μM ATP) using the phosphoacceptor peptide substrate FAM-GEEPLYWSFPAKKK-NH2.