BPN14770   Click here for help

GtoPdb Ligand ID: 10451

Synonyms: BPN-14770 | compound 28 [PMID: 31013090]
PDB Ligand
Compound class: Synthetic organic
Comment: BPN14770 is reported as a selective allosteric inhibitor of phosphodiesterase 4D (PDE4D) [3]. BPN14770 achieves isotype selectivity by binding to a single amino acid difference on the UCR2 regulatory domain of PDE4D that controls access of cAMP substrate to the enzyme's catalytic site. Dimeric isoforms of PDE4D appear to be important for normal brain function [2], with abnormally/inappropriately active isoform dimers being associated with intellectual disability [1].
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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

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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 3
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 50.19
Molecular weight 405.07
XLogP 5.83
No. Lipinski's rules broken 1

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 OC(=O)Cc1ccc(cc1)Cc1cc(nc(c1)C(F)(F)F)c1cccc(c1)Cl
Isomeric SMILES OC(=O)Cc1ccc(cc1)Cc1cc(nc(c1)C(F)(F)F)c1cccc(c1)Cl
InChI InChI=1S/C21H15ClF3NO2/c22-17-3-1-2-16(12-17)18-9-15(10-19(26-18)21(23,24)25)8-13-4-6-14(7-5-13)11-20(27)28/h1-7,9-10,12H,8,11H2,(H,27,28)
InChI Key LTSUMTMGJHPGFX-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
In contrast to the selectivity of BPN14770 for PDE4D isoform dimers, apremilast is equipotent (21-35 nM IC50s) against all of the dimer and monomer PDE4D isoform constructs tested by Gurney et al. [3].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
phosphodiesterase 4D Primary target of this compound Hs Allosteric modulator Negative 6.0 – 8.1 pIC50 - 3
⤷ pIC50 8.1 (IC50 7.4x10-9 M) [3]
Description: Inhibition of a fluorescent determination of reaction rate of cAMP hydrolysis by purified human PDE4D3-S54D dimer (activated).
pIC50 8.1 (IC50 7.8x10-9 M) [3]
Description: Inhibition of a fluorescent determination of reaction rate of cAMP hydrolysis by purified human PDE4D7-S129D dimer (activated).
pIC50 6.9 (IC50 1.27x10-7 M) [3]
Description: Inhibition of a fluorescent determination of reaction rate of cAMP hydrolysis by purified human PDE4D2 monomer,
pIC50 6.0 (IC50 1.018x10-6 M) [3]
Description: Inhibition of a fluorescent determination of reaction rate of cAMP hydrolysis by purified human PDE4D7-S129(wt) dimer (basal).