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
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 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
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 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
References
1. Briet C, Pereda A, Le Stunff C, Motte E, de Dios Garcia-Diaz J, de Nanclares GP, Dumaz N, Silve C. (2017)
Mutations causing acrodysostosis-2 facilitate activation of phosphodiesterase 4D3.
Hum Mol Genet, 26 (20): 3883-3894. [PMID:29016851]
2. Gurney ME. (2019)
Genetic Association of Phosphodiesterases With Human Cognitive Performance.
Front Mol Neurosci, 12: 22. [PMID:30800055]
3. Gurney ME, Nugent RA, Mo X, Sindac JA, Hagen TJ, Fox 3rd D, O'Donnell JM, Zhang C, Xu Y, Zhang HT et al.. (2019)
Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.
J Med Chem, 62 (10): 4884-4901. [PMID:31013090]