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    Integrated drug discovery services

    Integrated drug discovery

    Weak affinity screening technology

    Weak affinity chromatography

    Fragment-based lead generation

    Fragment library screening

    In silico lead discovery services

    In silico drug discovery

Integrated Drug Discovery Services

The integrated drug discovery and structure-based drug design (SBDD) platform at SARomics Biostructures offers fragment screening services, which include hit identification and hit-to-lead optimization for any target with known three-dimensional structure. Our extensive expertise in screening, computational chemistry and structure-based drug design is combined with the expertise of our in-house collaboration partner Red Glead Discovery to provide full-range discovery services including hit-to-lead optimization, assay development, medicinal chemistry and ADME.

Our services include:

Fragment library - Proprietary library design for easy hit expansion, specifically ordered sets and client libraries. Please enquire for details.

WAC™ screening technology - Our proprietary weak affinity chromatography (WAC™) screening technology allows simultaneous identification of weak binders (mM-μM) in complex mixtures, as well as Kd calculation. Offers include Pilot screen, Fragment screen and Ligandability screen.

Biophysical screening - Efficient hit identification using thermal-shift assay (DSF), isothermal titration calorimetry (ITC), Microscale thermophoresis (MST), NMR spectroscopy and X-ray crystallography.

Computational chemistry - Library design, hit expansion, pharmacophore- and shape-based virtual screening, scaffold hopping, QSAR analysis and optimization.

Structural biology - Highly efficient structural biology platform with proprietary high-throughput crystallization and structure determination protocols.

Medicinal chemistry - Through our collaboration with Red Glead we offer expertise in lead optimization, biological characterization, medicinal chemistry and ADME.

FOR DETAILS PLEASE SCROL DOWN!

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High Throughput Fragment Library Screening

The WAC™ method is based on covalent immobilisation of a protein to be screened on a standard high-performance liquid chromatograph (HPLC) column. The solution of small molecular weight fragments is subsequently injected into the column. During elution, the fragments that have higher affinity for the protein will stay on the column longer than those with low or no affinity. The fragments can be conveniently detected using mass or UV spectrometry. This method is an efficient and lower-cost choice, compared to other methods that study ligand binding, e.g., X-ray crystallography, NMR spectroscopy or isothermal titration calorimetry (ITC). After the initial hit identification, NMR spectroscopy and X-ray crystallography may be used to gain additional insights into the details of the interactions of the fragments with the protein binding site, the amino acid resides involved in the interactions, types of interactions, etc. Ligand efficiency and ligand binding energy may subsequently be calculated.

WACâ„¢ options offered

WAC™ pilot
Description

• Limited screen of small library < 50 fragments
• Client supply protein
• Preparation of column with immobilized protein
• Screening in duplicates
• Useful as feasibility step for large WAC™ screen
• Fixed price and fast turnaround

Deliverables
• List of hits sorted after Δt
ret
• Short report with technical details

Download pdf…

Proprietary fragment library
Our library includes a collection of 1300 fragments (available as neat sample, DMSO and DMSO-d6 solutions).
• Designed to be general purpose, (not target-directed) covering diverse chemical space.
• A focus on low-molecular weight fragments (<220)
• Solubility data (DMSO, water) are available for >80% of the fragments
• Analytical data (LCMS, 1H-NMR) available for all fragments
• Designed to be MedChem friendly (HBDs, HBAs and ring count, ClogP, functional groups, etc)
• >90% commercially available facilitating rapid SAR-generation

In silico Drug Discovery Services

Computational chemistry provides means for the combination of in silico methods, such as compound library screening, ligand docking, pharmacophore and shape-based virtual screening, scaffold hopping, QSAR analysis and optimization, providing substantial acceleration of the drug discovery process. Our virtual library used in in silico screening contains millions of purchasable compounds. It has already been pre-filtered to remove e.g. reactive groups and too-lipophilic compounds.
A more detailed outline of various drug discovery strategies, which can be designed depending on the type of information at hands, is discussed in our drug discovery technology pages.

Our in silico drug discovery services include (but are not limited to) the following options:

  • Pharmacophore and shape-based virtual screening
  • Ligand-based drug design
  • Scaffold hopping
  • Design of screening library
  • QSAR analysis and optimization

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