PRN694   Click here for help

GtoPdb Ligand ID: 9285

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: PRN694 is a small molecule, covalent inhibitor somewhat selective for the TEC family kinases, IL-2-inducible T cell kinase (ITK) and TXK tyrosine kinase (also known as resting lymphocyte kinase or RLK) [2-3]. In vitro PRN694 is a potent inhibitor of Th1 and Th17 differentiation and cytokine production (IFN-γ production for Th1 and IL-17A for Th17), and in vivo PRN694 markedly reduces disease progression in a mouse colitis model [2]. It is suggested that dual ITK and RLK inhibition may represent a novel therapeutic model for amelioration of Th1-mediated inflammatory diseases.
Mechanistically PRN694 inhibits kinase activity by binding irreversibly to cysteine residue 442 of ITK and 350 of RLK [3]. A series of compounds including PRN694 is claimed in patent WO2014036016 [1]. Example 29 is an enantiomer of PRN694 with one unspecified stereocenter.
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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 6
Hydrogen bond donors 2
Rotatable bonds 12
Topological polar surface area 107.5
Molecular weight 543.25
XLogP 4.3
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)N1CCCC1Cn1c(NC(=O)c2ccc(s2)C(F)F)nc2c1ccc(c2)CNC(C(C)(C)C)C
Isomeric SMILES C=CC(=O)N1CCC[C@@H]1Cn1c(NC(=O)c2ccc(s2)C(F)F)nc2c1ccc(c2)CN[C@H](C(C)(C)C)C
InChI InChI=1S/C28H35F2N5O2S/c1-6-24(36)34-13-7-8-19(34)16-35-21-10-9-18(15-31-17(2)28(3,4)5)14-20(21)32-27(35)33-26(37)23-12-11-22(38-23)25(29)30/h6,9-12,14,17,19,25,31H,1,7-8,13,15-16H2,2-5H3,(H,32,33,37)/t17-,19+/m0/s1
InChI Key NXTKFBGDLDPFLB-PKOBYXMFSA-N
Bioactivity Comments
In a kinase screening panel of 250 kinases ITK, TXK, BTK and BMX (all TEC family), and CLK2, CLK4, BLK, JAK3 and YES were the only enzymes inhibited by more than 90% at 1 μm PRN694 [3].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
IL2 inducible T cell kinase Primary target of this compound Hs Inhibitor Inhibition 9.5 pIC50 - 3
⤷ pIC50 9.5 (IC50 3x10-10 M) [3]
TXK tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 8.9 pIC50 - 3
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [3]
tec protein tyrosine kinase Hs Inhibitor Inhibition 8.5 pIC50 - 3
⤷ pIC50 8.5 (IC50 3.3x10-9 M) [3]
BMX non-receptor tyrosine kinase Hs Inhibitor Inhibition 7.8 pIC50 - 3
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [3]
Bruton tyrosine kinase Hs Inhibitor Inhibition 7.8 pIC50 - 3
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [3]
Janus kinase 3 Hs Inhibitor Inhibition 7.5 pIC50 - 3
⤷ pIC50 7.5 (IC50 3x10-8 M) [3]
BLK proto-oncogene, Src family tyrosine kinase Hs Inhibitor Inhibition 6.9 pIC50 - 3
⤷ pIC50 6.9 (IC50 1.25x10-7 M) [3]