Direct-to-Biology (D2B)

Discovering a Galaxy of Opportunity - Unleashing the power of plate-based chemistry combined with rapid screening

Unleash the full potential of our D2B expertise on your drug discovery project. Whether it’s to enable your Targeted Protein Degrader (TPD) project or supercharge your hit-to-lead (H2L) or lead optimisation (LO) programmes, Direct-to-Biology will open up a galaxy of opportunity for you! So, partner with Domainex and revolutionise your drug development process today.

Benefits of Direct-to-Biology (D2B) in Drug Discovery

Drug discovery is a complex and time-consuming process that requires the seamless integration of multiple disciplines and technologies. D2B has revolutionised the field by combining ‘plate-based chemistry’ with rapid biological screening. The key benefits of employing Domainex’s D2B expertise in your integrated drug discovery project include:

Plate-Based Chemistry:

Expert compound library design
- Computational design to increase chemical diversity
- Molecular modelling and in silico property predictions
- Assessment of scaffolds for plate-based chemistry
Accelerated compound synthesis
- For TPD projects: In-house ‘toolbox’ of partial PROTACs^® (PROTAC^® is a registered trademark of Arvinas Operations, Inc., and is used under license) available for immediate reaction with protein of interest (POI) binders
Not just amide couplings (see for example our blog on a two-step one-pot azidation-Cu-catalysed azide-alkyne cycloaddition reaction optimised for D2B)
Efficient resource allocation
Miniaturisation of reactions - Enhances efficiency and reduces environmental impact
High throughput purification can be included
Access to Domainex’s team of highly skilled synthetic chemists

Rapid Screening:

Customised assay development by our team of highly skilled biologists
- For TPD projects: Includes assessment of POI binding, ternary complex formation and the level of cellular protein degradation (e.g. Nano-Glo® and automated Western blotting)
Efficient hit validation
Early mechanism of action insights
De-risks development
Generates rapid SAR, including EPSA and ChromLogD
Allows data-driven decision making
Rapid optimisation of ADME properties

Domainex’s D2B Workflow

Up to 380 compounds can be generated in a single plate and screened using the workflow below:

Plate-based reaction optimisation is undertaken prior to D2B to ensure workflow efficiency and to minimise reagent usage.
Utilising this process, 1,000s of compounds can be synthesised and screened in less than 1 month
Automated QC and analysis, using UPLC MS, is conducted to allow a heat-map overview to be produced to assess the quality of each plate (see Figure 1)
Hits can be observed even when a relatively low sample purity is observed.

Direct to Biology plate map graphic — **Figure 1:** Automated QC analysis & evaluation in degradation assays. (A) A heat map of compound purity (automated UPLC-MS) generated by PyParse, (B) D2B assay readout for 4 compounds; levels of cellular protein degradation *(Nano-Glo®) and automated Western blotting showing concentration dependent TPD.*

D2B combines plate-based chemistry with rapid screening, synergistically enhancing the efficiency and success of drug discovery. These methods allow researchers to explore rapidly chemical space, identify hits, validate their biological activity, gain early insights into mechanism of action and asses the ADME properties, ultimately streamlining the development of novel and effective therapeutics. By embracing these cutting-edge techniques, Domainex will accelerate your drug discovery programmes and help you to bring life-changing medicines to patients more efficiently and effectively.

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Unleash the full potential of our D2B expertise on your drug discovery project. Whether it’s to enable your Targeted Protein Degrader project or supercharge your hit-to-lead or lead optimisation programmes, Direct-to-Biology will open up a galaxy of opportunity for you!

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