Direct-to-Biology (D2B)

Accelerating experimental learning in drug discovery

Direct to biology logo

Direct-to-Biology (D2B) is an increasingly adopted drug discovery approach that combines high-throughput chemistry, rapid biological screening and integrated data analysis to accelerate Design-Make-Test-Analyse (DMTA) cycles. D2B enables hit identification, hit-to-lead, and lead optimisation programmes to progress faster by generating biological and developability data directly from plate-based synthesis campaigns.

At Domainex, we combine plate-based chemistry, integrated biological screening, early ADME profiling and machine learning-assisted data analysis to help drug discovery teams make better decisions, faster. Whether you're developing targeted protein degraders, covalent inhibitors, molecular glues, fragments or traditional small molecules, our D2B platform enables rapid exploration of chemical space while significantly reducing timelines and reagent consumption.

 

Why Direct-to-Biology?

Drug discovery increasingly demands rapid experimental validation of large numbers of design hypotheses. While computational methods continue to improve, experimental data remains essential for driving decision making.

D2B addresses this challenge by combining synthesis and screening into a highly efficient workflow that delivers:

 

Speed - Generate and screen hundreds to thousands of compounds in a matter of weeks.

Accelerated Learning - Rapidly establish SAR and identify productive design directions.

Reduced Material Consumption - Typical reactions utilise only nanomole quantities of reagents, reducing material costs and environmental impact.

Bespoke Chemical Space - Create tailored libraries designed specifically around your target, rather than relying solely on commercial screening collections.

Faster Decision Making - Obtain biological and developability data earlier, allowing project teams to focus resources on the most promising compounds.

Impact of D2B - allows skipping the slow purification step of chemical synthesis. Results in faster DMTA cyc;les, less reagents used, reduced cost, improved efficiency and lower environmental impact

Direct-to-Biology Platform for Rapid DMTA Cycles

Our integrated D2B platform brings together computational design, automated synthesis, high-throughput screening and advanced data analytics to accelerate lead discovery and optimisation.

Accelerating Design-Make-Test-Analyse (DMTA) Workflows

Phase 1 - Design
Phase 2 - Make
Phase 3 - Test
Phase 4 - Analyse
Library Design
  • Structure-guided and computationally informed library generation
  • Access to curated D2B building block collections
  • Property-driven compound prioritisation
D2B Synthesis
  • Plate-based synthesis using nanomole-scale chemistry
  • Single-step and multi-step reaction workflows
  • Automated QC using UPLC-MS
Biological Screening
  • Biophysical, biochemical and cellular assay platforms
  • Rapid identification of active compounds
  • Early mechanism-of-action insights
ML-Assisted Analysis
  • Efficient analysis of large datasets
  • Rapid SAR generation
  • Informed progression decisions

AI-Enabled Drug Discovery Requires Rapid Experimental Validation 

Artificial intelligence and machine learning are transforming compound design by enabling the rapid generation of thousands of chemical hypotheses. The challenge is no longer generating ideas  but rapidly determining which ideas merit further investment.

Domainex's Direct-to-Biology platform provides the experimental engine required to validate AI-generated hypotheses, enabling rapid Design-Make-Test-Analyse (DMTA) cycles that transform predictions into actionable biological data.

By combining computational design, D2B synthesis, biological screening and machine learning-assisted analysis, we help clients rapidly identify promising chemical series and focus resources on the most productive areas of chemical space.

D2B-Compatible Assay Platforms

BioAssayCompatibility with Reaction Type
Amide CouplingSuzuki CouplingReductive AminationBuchwald-HartwigSN2/SNArCuAAcPhotoRedoxAmide–Suzuki–de‑Boc

GCI/SPR

YesYesYesYesNot testedNot TestedNot TestedNot Tested

Spectral Shift

YesYesYesYesNot testedNot TestedNot TestedNot tested

HiBiT

YesYesYesYesYesYesYesYes

Intact Mass Spectrometry

YesNot testedNot testedNot testedNot testedNot testedNot testedNot tested

Flow Cytometry

YesNot testedNot testedNot testedNot testedNot testedNot testedNot tested

CellTitre-Glo®

YesYesYesYesYesYesYesYes

Microsomal Clearance

YesYesNot testedNot testedNot testedNot testedNot testedNot tested

Multi-Step D2B Chemistry

One of the key advances in Domainex's D2B workflows is the ability to undertake multi-step reaction sequences directly within a plate-based format. This allows for rapid generation of more complex molecules for screening.

Multistep reactions compatible with direct-to-biology (D2B) for rapid generation of complex molecules

D2ADME: Early ADME Profiling from Direct-to-Biology Campaigns

Potency alone is rarely enough to progress a compound.

Domainex's D2ADME platform extends the value of D2B campaigns by allowing the collection of key drug property data directly from screening samples.

Available D2ADME Readouts

This provides early insight into compound developability while helping teams prioritise molecules with the best balance of potency and drug-like properties.

Benefits

  • No purification required
  • Compatible with multiple reaction classes
  • Additional value from existing screening samples
  • Supports faster project progression and resource allocation
Domainex Direct to ADME (D2ADME) - ChromlogD, Miscrosomal stability and TPSA from crude reaction mixtures

Quality Built Into Every Campaign

Scientist working in glove box on direct to biology project

Speed is valuable only when paired with quality.

Our D2B workflow includes:

  • Plate-based reaction optimisation
  • Automated UPLC-MS analysis
  • Compound quality heat-map generation
  • Data-driven progression criteria
  • Hit confirmation via resynthesis and purification

This rigorous approach ensures confidence in the biological data generated throughout a D2B campaign.

Why Choose Domainex?

Domainex provides a fully integrated Direct-to-Biology platform that combines medicinal chemistry, biological screening, ADME profiling and data-driven decision making to accelerate drug discovery.

  • Extensive single-step and multi-step D2B chemistry
  • Integrated biology, biophysics and screening expertise
  • Dedicated D2ADME capabilities
  • Proprietary D2B building block collections
  • Computationally guided library design
  • Machine learning-assisted data analysis
  • Expertise across PROTACs, molecular glues, fragments, covalent inhibitors and small molecules
  • Flexible project design tailored to your programme

Our scientists work across chemistry, biology and data science to ensure every D2B campaign delivers meaningful insights that accelerate discovery.

Download the Brochure

D2B brochure front cover

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!

Download brochure

Frequently Asked Questions

What is Direct-to-Biology (D2B)?

Direct-to-Biology (D2B) is a drug discovery approach in which compounds are synthesised and tested directly in biological assays without the need to purify every individual sample. By reducing purification bottlenecks, D2B enables scientists to explore larger areas of chemical space and generate biological data more rapidly.

Why has there been so much interest in D2B over the last few years?

The volume of ideas that can be generated through computational chemistry, virtual screening, structure-based design and AI has increased dramatically. The challenge is no longer generating hypotheses, but determining which ones deserve further investment.

Domainex addresses this challenge by using D2B to accelerate experimental learning and enabling faster project decisions.

What types of drug discovery programmes can benefit from D2B?

Domainex has successfully applied Direct-to-Biology (D2B) across a wide range of discovery modalities, including:

Projects that require rapid exploration of large design spaces tend to benefit most from D2B approaches.

Can data generated from crude reaction mixtures be trusted?

Yes, provided appropriate controls are in place.

D2B workflows at Domainex routinely incorporate compatibility testing, orthogonal validation approaches and analytical controls to ensure reliable biological data can be generated from crude samples.

The discussion has increasingly shifted from “Can D2B data be trusted?” to “How can D2B data be used most effectively?”

What types of biological assays are compatible with D2B?

The range of compatible assays continues to expand.

Examples of D2B-compatible biological assays used by Domainex include:

This allows biologically meaningful questions to be addressed much earlier in the discovery process.

What chemistry can be performed using D2B?

Early D2B campaigns focused heavily on robust reactions such as amide coupling and CuAAC chemistry.

Today, successful examples used by Domainex include:

  • Amide coupling
  • CuAAC
  • SuFEx
  • Reductive amination
  • SNAr chemistry
  • Alkylation
  • Suzuki coupling
  • Buchwald-Hartwig coupling

The reaction toolbox continues to expand as more medicinal chemistry transformations are adapted to D2B workflows.

How does Domainex use AI and machine learning complement D2B?

Domainex uses AI to help generate and prioritise molecular hypotheses, while D2B provides the experimental feedback needed to evaluate them quickly.

Together, they create a powerful combination: AI suggests what to make, and D2B helps determine which compounds are worth pursuing.

Machine learning is increasingly being used to analyse and interpret D2B datasets.

Examples include identifying false negatives, separating low reaction yield from weak biological potency and helping researchers extract more insight from large D2B screening campaigns.

What are the biggest remaining challenges for D2B?

The greatest challenges now lie on the chemistry side.

Although reaction scope has expanded considerably, some chemistry still does not achieve the robustness of established D2B reactions such as amide coupling, CuAAC and SuFEx chemistry.

Late-stage functionalisation is also likely to become an important area of future development.

When should I consider using D2B?

Domainex has found that D2B is particularly valuable when:

  • Large numbers of compounds need to be assessed rapidly
  • SAR information is limited
  • Design spaces are large or complex
  • Fast DMTA cycles are important
  • Resources need to be focused on the most promising compounds
How does Domainex support D2B projects?

Domainex has been investing in D2B technologies, workflows and research for several years and applies D2B approaches across a growing number of client programmes.

Our integrated capabilities in medicinal chemistry, biology, biophysics, structural biology and ADME allow us to deploy D2B where it can generate the greatest value, helping clients accelerate learning, improve decision-making and progress programmes more efficiently.

What does the future of D2B look like?

The future of D2B is unlikely to be defined simply by faster chemistry.

Domainex scientists envision that future D2B experiments will be characterised by increased integration with:

The overarching goal remains the same: helping discovery teams learn faster and identify better drug candidates sooner.