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Phosphodiesterase (PDE10) Targeted Library

Phosphodiesterases are a family of enzymes that regulate cyclic nucleotide signaling by degrading the second messenger molecules: cGMP and cAMP. Disturbances of basal ganglia process is closely associated with schizophrenia, and phosphodiesterase 10A is a dual cAMP/ cGMP phosphodiesterase that is expressed at high levels in the striatal medium spiny neurons. It has been widely used to find effective and selective treatments for degenerative central nervous system disorders, and is studied as a therapeutic target for certain psychiatric and neurological disorders. Therefore, a variety of PED10A inhibitors are currently being evaluated in clinical trials for the treatment of schizophrenia. In addition, PDE10 has been demonstrated to have a novel role in colon tumorigenesis, and its inhibitors may be used to treat or prevent colorectal cancer.

BOC Sciences has designed its unique phosphodiesterase PDE10 screening library, providing 1,450 potential phosphodiesterase PDE10 inhibitors.

PDE10 signaling in colon cancer. Figure 1. PDE10 signaling in colon cancer. (Lee, K.; et al. 2016)

Phosphodiesterase (PDE10) Targeted Library Design

BOC Sciences has developed a unique method for in silico search of small-molecule screening compounds with potential PDE10 inhibitory activity by combining different computational approaches.

  1. In the first stage, multiple available X-ray structures of PDE10 in complex with small molecule phosphodiesterase inhibitors are obtained from various database
  2. Then, we apply diversity analysis to filter some of the most similar structures
  3. Finally, a series of 3D pharmacophore models (in addition to ligand features, PDE10A active site boundaries are included) are generated for screening against the BOC Sciences HTS compounds collection
  4. In the second phase, approximately 10,000 virtual screening hits produced from the first stage are used for the subsequent molecular docking. BOC Sciences supports a Glide docking procedure in the Schrödinger software which is performed on the basis of 3 conformationally different PDE10A structures
  5. Finally, 1,450 potential phosphodiesterase PDE10 inhibitors with the highest scores and structural diversity are delivered after docking and manual inspection of complexes

PDE10 inhibitors induce downstream kinase signaling.  Figure 2. PDE10 inhibitors induce downstream kinase signaling. (Lee, K.; et al. 2016)

Phosphodiesterase (PDE10) Targeted Library Characteristics

  • High diversity over the screening set: mean Tanimoto > 0.85
  • Favorable physicochemical parameters and solubility requirements
  • No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
  • Bioactivity and safety confirmed by preclinical studies and clinical trials
  • Structural diversity, medicinal activity, and cellular penetration
  • Structural document, IC50, and other chemical and biological data are provided
  • All compounds are continually updated
  • Compound cherry-picking service is provided

What We Deliver

  • Delivered within 2 weeks in any customer-preferred format
  • Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
  • All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
  • Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Phosphodiesterase (PDE10) Targeted Library design at competitive prices for global customers. Personalized and customized services of Phosphodiesterase (PDE10) Targeted Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!

Reference

  1. Lee, K.; et al. β-catenin nuclear translocation in colorectal cancer cells is suppressed by PDE10A inhibition, cGMP elevation, and activation of PKG. Oncotarget. 2016. 
Our mission is to provide clients with a professional chemical library design platform. Empowered by high-quality services and effective research solutions, we are committed to helping customers achieve effective and successful research goals.

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Services Based on the Chemical Library Design Platform

Services Based on the Chemical Library Design Platform

BOC Sciences has rich experience in working with global customers in custom library synthesis of compounds and generating small to medium-sized libraries of target compounds. Our knowledge in generating a large number of target molecules in a remarkably shorter time enables quick biological screenings for affinities. With the target properties in mind, we deliver target molecules, by applying our extensive knowledge in drug discovery.

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