Drug R&D Services & Solutions

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Drug R&D Services & Solutions

  • visibility Read 2002 times


    • Spillo background
    Key drivers in improving the performance of pharmaceutical companies

    SPILLOproject provides a spectrum of specific services aimed at optimizing various phases of the drug discovery and development process. 

     

     

    By means of SPILLO-PBSS we can analyse the whole structural proteome of Homo sapiens and other organisms (e.g., Mus musculus, Rattus norvegicus) to highlight the potential target and off-target proteins of any small-molecule. In fact, in addition to the experimentally solved protein structures available from the RCSB Protein Data Bank (corresponding to approximately 40% of the human proteome), since July 2021 we also have the possibility to analyse the artificial intelligence (AI) predicted AlphaFold Protein Structure Database (corresponding to about 100% of the human proteome).

     

    ORGANISM Protein 3D-structures
    RCSB Protein Data Bank
    Solved by X-ray diffraction, solution NMR, cryo-EM
    (with redundancies)
    		 AlphaFold Protein Structure Database
    Predicted by AI (Released in: July 2021)
    (without redundancies)
    Homo sapiens

    55,280+

    Structural coverage of the human proteome: ~ 40%

    23,390+

    Structural coverage of the human proteome: ~100%
    Mus musculus 7,790+ 21,600+
    Rattus norvegicus 3,480+ 21,270+
    Total: 66,550+ (April 2022) 66,260+ (July 2021)

     

    Structural details concerning the location of the potential binding sites on the protein structures and the relative 3D-orientation of the molecule are also provided by the analysis.

     

    Services provided by SPILLOproject What is this information used to?
    (A) Identification of target proteins responsible for (known) therapeutic effects of small molecules (e.g., drugs under development, drugs already on the market, active constituents of traditional medicine) - to increase the binding affinity between the small molecules and the target responsible for their therapeutic effects (Rational Drug Design)
    - to select small molecules able to interfere with multiple drugs of the same pathological network (Polypharmacology)
    - to develop tests able to predict patient response to a specific treatment, with the aim of choosing the most effective treatment based on the individual characteristics of the patient (Precision medicine)
    - etc.
    (B) Identification of off-target proteins responsible for (known) adverse effects of small molecules (e.g., drugs under development, drugs already on the market) - to decrease the binding affinity between the small molecules and the off-targets responsible for their adverse effects (Rational Drug Design)
    - to develop tests able to predict patient response to a specific treatment, with the aim of choosing the safest treatment based on the individual characteristics of the patient (Precision medicine) 
    - etc.
    C) Identification of target proteins responsible for (novel) therapeutic effects of small molecules - to find new uses for drugs already on the market (Drug repurposing)
    - to find new uses for drugs under development and archived because found ineffective, although safe (Drug rescuing)
    - etc.
    (D) Identification of off-target proteins responsible for (still unknown) adverse effects of small molecules (e.g., drugs under development, drugs already on the market) - to early identify potential drug safety-related issues and prevent late-stage failures (De-risking strategy - Attrition rate reduction)
    - to acquire more information concerning the safety of drugs already on the market and allow a safer use for the patients
    - etc.
    (E) Assessment of the selectivity of drugs under development as a function of the number of their off-target proteins (inverse correlation).  - to prioritize drugs under development according to their selectivity (De-risking strategy - Attrition rate reduction)
    - etc.