Hit identification

The identification of high quality hit matter is critical to the success of any small molecule drug discovery program. Our medicinal chemistry, bioscience and computational chemistry teams work together in collaboration with our clients to determine the best hit finding technique for their project.

We have successfully identified novel hit series for a variety of different target classes using virtual, biochemical, phenotypic and biophysical screening techniques, all of which are backed up by scientists with a high level of experience and expertise.

Important information: Aurelia Bioscience website pages now redirect to Charnwood Molecular following the company’s acquisition. If you have any questions about our bioscience services or specific content you are looking for please contact   info@charnwood-molecular.com

Hit identification (chemistry)

  • Using in-house expertise and data analytical tools such as Stardrop, our experienced medicinal chemists efficiently evaluate the output from a High Throughput Screen (HTS) or targeted screen to identify promising chemical series with properties suitable for further optimisation
  • Series are evaluated and prioritised for synthetic effort based upon synthetic tractability, appropriate physical chemical properties and ligand efficiency metrics
  • Re-synthesis of HTS “actives” is recommended to provide fully characterised compounds which enables confirmatory biological retesting and preliminary ADME screening to provide additional confidence to commence a synthetic hit to lead programme
  • We also provide activity confirmation through compound resynthesis, in addition to hit triage. This is based on our experience of drug-like properties, followed by early exemplification (i.e., analogue-by-catalogue or wet chemistry) to provide initial SAR and clearly define the hit expansion strategy

Hit identification (biology)

  • We develop both cell-based and biochemical bio-assays for your high throughput screening needs using state of the art readouts, such as high content imaging, in addition to fluorescence and luminescence outputs
  • Most assays are performed in 384 well plates with relevant controls on each plate for quality control using statistical rigor as standard
  • Using appropriate software we are able to triage compounds and apply a cut-off in order to select the most appropriate compounds for retest and subsequent dose-response
  • Either at the retest or dose-response stage we introduce selectivity and specificity assays in order to identify the most appropriate pharmacophores for further chemisty iteration

Time saving approach

A key benefit for our clients is our computational chemistry capability.

Our computational chemists use the Schrodinger Small Molecule Drug Discovery Suite in conjunction with the latest releases of the Enamine and MolPort virtual screening libraries. These libraries can be enumerated to many millions of compounds for virtual screening, depending upon the nature of the target and the property space in which we chose to work.

With hits in hand, our computational chemists use modern machine learning (ML), quantum mechanics (QM), molecular dynamics (MD) and fragment molecular orbital (FMO) approaches to enhance our understanding of the way in which a particular hit series interacts with a protein of interest.

For structure-based drug discovery projects, this information can be used to rationalise structure activity relationships, differentiate between different hit series and inform decision making in support of our medicinal chemistry design teams, as they move around an iterative design-make-test-analyse cycle.

For our clients, this translates to an increase in the efficiency with which we can identify high quality hit matter against their target and move their project forward towards the next important milestone.

Our co-located bioscience team can interface with computational chemistry to rapidly test a library of compounds and provide data to iterate the design-make-test cycle

We can introduce other assay readouts at this stage to move from a biochemical to a cell-based assay or from a recombinant cell-based assay into a human primary cell-based assay with lower throughput but a more physiological readout.

Our experienced scientists are able to multitask on your project to maintain a number assays in a state of readiness for profiling your compounds.

Virtual screening (computational chemistry)

Our computational chemistry team has access to the latest versions of the Enamine and MolPort screening libraries, which can be enumerated to many millions of compounds, depending upon the nature of the target and the needs of the client, for virtual screening against a target of interest.

They can filter and cluster the output from their virtual screening process according to a variety of different options. They can also use quantum mechanics (QM) and frontier molecular orbital (FMO) approaches to better understand the way in which a specific series interacts the protein of interest, which can inform decision making around series selection and hit expansion.

We have successfully conducted several virtual screening campaigns on behalf of our clients, which have resulted in the identification of novel sub-micromolar chemical series that have been verified using wet screening techniques, highlighting the power of this approach.

Biophysical instrumentation

The speed at which a hit is identified is critical in the drug discovery process. Investment in  market leading instrumentation enables us to provide the speed of service our clients require without sacrificing quality.

Extensive benchmarking  of relevant instruments is conducted before any investment is made. Purchase of the Biacore 8K high-throughput, high-sensitivity SPR system allows us to deliver efficient screening, characterisation, process optimisation, and quality control of small molecules and biotherapeutics.

Our track record

Our experienced team has successfully identified novel hit series for a variety of different target classes using virtual, biochemical, phenotypic and biophysical screening techniques, all of which are backed up by scientists with a high level of experience and expertise.

Take a look at an example of our work in this area with the following case study:

You can also download our eBook on developing effective assays:

Our success stories

View all case studies