Fragment-Based Drug Discovery Services

Fragment screening, hit expansion & lead generation

SARomics Biostructures' fragment-based drug discovery services offer access to our proprietary weak-affinity chromatography (WAC™) screening technology the commercial rights of which are jointly owned by us and our in-house partner Red Lead Discovery.

Our services include:
  • Fragment screening and hit identification (proprietary library or custom library)
  • Hit expansion, hit-to-lead generation and lead optimization
  • Biochemical and cell-based assay and in vitro ADME
  • Computational chemistry
  • Structure-based drug design (SBDD)

Our structure-based drug design include hit-to-lead optimization and is guided by
X-ray crystallography and determination of the structure of the protein in complex with the compounds of interest.
Together with WAC™
screening, if required we provide biophysical screening techniques for hit identification, such as thermal-shift assay (DSF), isothermal titration calorimetry (ITC) and NMR spectroscopy.

For details of the services please follow the links below.

Weak-affinity chromatography

FastLane Premium Library of X-ray structures of drug targets
At the center of our integrated drug discovery and structure-based drug design services is the high throughput (2000-3000 cmpds/week) proprietary weak-affinity chromatography (WAC™) screening technology, which provides high quality data and has been validated against NMR spectroscopy and X-ray crystallography.

Proprietary fragment library

FatLane standar library of X-ray structures of drug targets
We suggest our fragment library with a collection of 1300 low-mw (<220) MedChem friendly compounds (available as neat sample, DMSO and DMSO-d6 solutions), designed to be general purpose (not target-directed) covering diverse chemical space. Custom libraries can also be run.

Computational chemistry services

gene-to-structure services by SARomics Biostructures
Structure-based drug discovery projects are efficiently aided by a wide range of computational chemistry services, including:
  • Pharmacophore and shape-based virtual screening
  • Ligand-based drug design
  • Scaffold hopping
  • QSAR analysis and optimization
Some answers to possible questions related to structure-based drug discovery strategies may be found in our Learning Center and may help you in the design of your project. Or just contact us for a presentation of the details of our services and for a discussion of your project.

WAC™ screening technology

WAC™ Facts

  • Screening and binding assay in one experiment
  • Measure fragment affinity to immobilized protein
  • Built-in quality control (MS)

WAC™ Key Advantages

  • Robust and accurate (validated against NMR and X-ray)
  • Quick set-up and workflow (3 weeks turnaround)
  • High throughput (>5000 cmpds/week)
  • Low material consumption (<5 mg protein)
  • Find mM hits by screening fragments at low concentration (1-5 μM)
  • Hit rates from 1% to 20%, (avg 6%)
  • Output – High quality data for MedChem

WAC™ Applications

  • Screen for novel chemical starting points
  • Assess druggability of new targets
  • Find differentiated backups in mature projects
  • Rescue mode for challenging targets (PPI etc.)

Basics of WAC™ screening technology

WAC™ is the primary fragment screening method used within our integrated drug discovery services program. It is based on covalent immobilisation of the protein to be screened on a standard high-performance liquid chromatography (HPLC) column. A solution of small molecular weight fragments or larger compounds is injected into this 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 biophysical screening methods that study ligand binding, e.g., X-ray crystallography, protein NMR spectroscopy or isothermal titration calorimetry (ITC).

After the initial hit identification,
NMR spectroscopy (sometimes called BioNMR) or X-ray crystallography can be used to gain additional insights into the details of the interactions of a compound with the protein. Ligand efficiency and ligand binding energy may also be estimated to guide hit expansion, lead generation and lead optimization.
The commercial rights of WAC™
are jointly owned by Red Glead Discovery and SARomics Biostructures.

Proprietary fragment library

Our fragment library includes a collection of 1300 compounds (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)

  • More than 90% commercially available facilitating rapid SAR-generation

Klara Jonasson, Red Glead Discovery
On the image: Klara Jonasson, PhD,
Senior Research Scientist, Red Glead Discovery

Computational chemistry & in silico drug discovery services

Computational chemistry methods can be efficiently used in integrated drug discovery and they are essential in structure-based drug design. It provide means for the combination of pharmacophore and shape-based screening of fragment or larger compound libraries, ligand docking, scaffold hopping, QSAR analysis and ligand optimization, allowing substantial acceleration of the 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 compounds that are too lipophilic.
A discussion of the details of various
drug design strategies, which can be followed depending on the type of information at hands, may be helpful in planing a discovery project.
Our computational chemistry and in silico drug discovery services include (but are not limited to) the following options:

  • Pharmacophore and shape-based virtual fragment screening
  • Ligand-based drug design
  • Scaffold hopping
  • Design of screening library
  • QSAR analysis and optimization
computational chemistry services, in silico screening and drug design
As part of our computational chemistry services, we also offer protein optimization and structure-based design of biological drugs (biologics) and peptides using quantitative structure-activity relationships (QSAR) methodology as implemented in our proprietary ProPHECY™ software package.
Bo Svensson, Computational Chemistry, SARomics Biostructures
On the image: Bo Svensson, PhD, Director, in silico discovery

Our publications are our best testimonials!

Korkmaz B, Lesner A, Wysocka M, Gieldon A, Håkansson M, Gauthier F, Logan DT, Jenne DE, Lauritzen C, Pedersen J (2019). Structure-based design and in vivo anti-arthritic activity evaluation of a potent dipeptidyl cyclopropyl nitrile inhibitor of cathepsin C. Biochem Pharmacol. 164, 349-367.

Gustafsson NMS, Färnegårdh K, Bonagas N, Ninou AH, Groth P, Wiita E, Jönsson M, Hallberg K, Lehto J, Pennisi R, Martinsson J, Norström C, Hollers J, Schultz J, Andersson M, Markova N, Marttila P, Kim B, Norin M, Olin T, Helleday T (2018). Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination. Nat Commun. 9, 3872. DOI: 10.1038/s41467-018-06287-x

Pippione AC, Federico A, Ducime A, Sainas S, Boschi D, Barge A, Lupino L, Piccinini M, Kubbutat M, Contreras J-M, Morice C, Al-Karadaghi S and Lolli ML. (2017). 4-Hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide: a novel inhibitor of the canonical NF-κB cascade. Med. Chem. Commun. 8, 1850–1855. DOI: 10.1039/c7md00278e

For a full list please visit our publications list.

For related services please follow the respective link

protein X-ray crystallography services, gen-to-structure and off-the-shelf structures

X-ray crystallography

protein NMR spectroscopy services, fragment screening and ligand binding

Protein NMR spectroscopy

antibody and antibody-antigen complex strucure charaterization, high order structure of biosimilars

Antibody structure

Structure-based design of biological drugs