Lead Optimization

The lead optimization stage involves testing a small number of compounds, identified in the hit-to-lead stage, across a wide range number of assays to improve biological activity, potency and selectivity, whilst reducing potential toxicity.

Further evaluation of the compounds is conducted to understand how they are absorbed, distributed, metabolized, and eliminated during pre-clinical trials.

Application of bioassays that are more relevant to assay biology is conducted using a number of different bioassay readouts including high content, flow cytometry, and Western blotting with relevant human cells and samples.

Studies are carried out to identify relevant biomarkers for the disease and/or look at target expression in tissue isolated from in-vivo studies.

Our services
Rational Design
HitChem's lead optimization service integrates the expertise of our diverse team to provide customized, innovative solutions for drug development. With deep knowledge in medicinal chemistry, computational design, and structural biology, our experts craft tailored strategies that align with the unique needs of your project. We deliver original compound designs that not only improve potency and selectivity but also create valuable intellectual property (IP) opportunities, minimizing Freedom to Operate (FTO) risks. Leveraging advanced computational techniques such as Free Energy Perturbation (FEP) and Molecular Dynamics (MD) simulations, we refine molecular designs with precision. Our in-house chemistry lab facilitates rapid synthesis and testing, enabling an accelerated DMTA (Design, Make, Test, Analyze) cycle. This streamlined approach ensures faster progression through lead optimization, bringing you closer to high-quality drug candidates.
2D Molecule Generation
HitChem's 2DMG, an advance model which sparks creativity in medicinal chemistry experts, accelerating the drug discovery process by generating diverse 2D molecular structures. The model is pretrained on a vast dataset comprising 30 million commercial compound structures (covering most global commercial compounds), 8 million patent-derived compound structures (spanning from the 1960s to 2023), 11 million building block structures, and billions of easily synthesizable molecular structures. This large-scale training enables the generation of drug-like molecules suitable for focused library generation and rational design.
Key Features
  ● Rapid synthesis & Biological validation
  ● IPfree chemical space   ● Customized solutions   ● Expert team
● Accelerated DMTA cycle
Deliverables
● Raw data

  ● Detailed reports: detailed summaries of methods, results, and analyses

  ● Visual analysis: visual representation and molecular interaction diagrams

  ● Selected compound list

Lead optimization case study