6MSC

Novel, potent, selective and brain penetrant phosphodiesterase 10A inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.36 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors.

Geneste, H.Drescher, K.Jakob, C.Laplanche, L.Ochse, M.Torrent, M.

(2019) Bioorg Med Chem Lett 29: 406-412

  • DOI: https://doi.org/10.1016/j.bmcl.2018.12.029
  • Primary Citation of Related Structures:  
    6MSA, 6MSC

  • PubMed Abstract: 

    Herein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3.


  • Organizational Affiliation

    AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, D-67008 Ludwigshafen, Germany. Electronic address: herve.geneste@abbvie.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
A, B
332Homo sapiensMutation(s): 0 
Gene Names: PDE10A
EC: 3.1.4.17 (PDB Primary Data), 3.1.4.35 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y233 (Homo sapiens)
Explore Q9Y233 
Go to UniProtKB:  Q9Y233
PHAROS:  Q9Y233
GTEx:  ENSG00000112541 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y233
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.36 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.53α = 90
b = 81.81β = 90
c = 159.4γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2019-01-09 
  • Deposition Author(s): Jakob, C.G.

Revision History  (Full details and data files)

  • Version 1.0: 2019-01-09
    Type: Initial release
  • Version 1.1: 2019-02-06
    Changes: Data collection, Database references
  • Version 1.2: 2024-03-13
    Changes: Data collection, Database references, Derived calculations