4 Ways Medicinal Chemists Power Drug Discovery and Development

Medicinal chemists improve the quality of compounds to boost the chances of clinical trial success and expand treatment options for patients.

Despite advances across the pharmaceutical sector, merely one-third of the estimated 30,000 known diseases can be treated. We need new medicines, and medicinal chemists help lead and optimise the drug discovery and development process to create them. 

Read on to find out:

• What medicinal chemistry is
• 4 ways medicinal chemists power drug discovery
• Key skills of a medicinal chemist

What is medicinal chemistry?

Medicinal chemistry is an interdisciplinary science that combines chemical biology, pharmacology, and medicine to drive drug discovery. 

Medicinal chemists help to discover new lead compounds for new medicines, demonstrate how well biological targets bind with the lead compound (target druggability), and address issues that determine drug success, safety, and failure. By improving the quality of drug candidates, medicinal chemists help to maximise the chances of clinical trial success.

4 ways medicinal chemists power drug discovery

1. Lead compound discovery

Lead compounds are chemicals with therapeutic biological activity against a target for a particular disease.

Lead compound discovery is often a collaborative affair that medicinal chemists guide with their research and expertise.

Medicinal chemists scour large libraries of potential compounds using either classical combinatorial chemistry, or computer modelling in-silico techniques – the more compounds that are screened, the greater the chance of success. 

Medicinal chemists use often more than one screening technique to find the most lead compounds with optimal success potential. Machine learning, including deep learning and AI, show promise when it comes to increasing the efficacy of this process. 

Partnering with Exscientia, Sanofi are using cutting edge AI techniques to identify new lead compounds for treatments within oncology and immunology. Exscientia’s ‘Centaur Chemist’ is helping Sanofi’s medicinal chemists and wider team accelerate this process by computationally sifting through and comparing millions of small molecules before selecting the most viable candidates for synthesis, testing and optimisation. 

2. Compound synthesis

Medicinal chemists use synthetic procedures to create compounds for new medicines, and to re-synthesize screening hits for biological evaluation. 

Medicinal chemists usually synthesize compounds using legacy reactions that generate structurally similar compounds, however change is on the horizon. Synthesis innovation is of growing importance to many pharmaceutical companies, including GlaxoSmith Kline who have initiated collaborative relationships with the Engineering and Physical Sciences Research Council to expand the diversity scope of reactions used in synthesis.

Once developed, these new reactions will offer medicinal chemists new pathways to synthesizing diverse compounds, without taking away time to explore new reaction conditions.

3. Compound design

Medicinal chemists specialise in compound design, where they help to balance and combine the competing parameters of structure and biological function. 

Compound quality is an increasingly critical area of concern across pharma, where diminishing success rates of clinical compounds are driving attrition in development. Industry research has paved the way for more thorough design parameters for the benefit of medicinal chemists, including:

• The rule of 3 
• Ligand efficiency 
• Predictive models 

These parameters and heuristics are now routinely integrated within compound design by medicinal chemists to reduce late-stage attrition in drug development.

4. Discovering and selecting targets

A target can refer to a range of biological forms including proteins, genes and RNA. 

Targets are linked to a disease process and are targeted by the chemical compounds within a drug to produce a therapeutic effect. Medicinal chemists help guide the identification of safe, efficacious targets that are accessible to the drug molecule. 

Medicinal chemists discover potential targets by:

• Data mining – where biomedical data including publications, patent information, gene expression data, proteomics data, transgenic phenotyping and compound profiling data are scoured using AI software to identify viable targets.
• Establishing correlations – where chemists examine mRNA/protein levels to determine whether they are a product of the disease, and if they are correlated with disease progression.
• Genetics association – where medicinal chemists look for links between genetic elements and risk of disease, or disease progression. 

Once a potential target is identified, medicinal chemists use validation processes to select the most appropriate and safe targets connected to the disease area. 

Skills for success as a medicinal chemist

Medicinal chemists have an important role to play across drug discovery and development, where their expertise and experience helps to activate and enable success. 

Key skills include:

1. A thorough knowledge of modern organic chemistry and medicinal chemistry
2. An understanding of related biology to the target disease area
3. Experience with pharmacological tests
4. Knowledge of the factors that influence chemicals in vivo
5. Current knowledge of competitive and emerging technologies
6. An entrepreneurial attitude
7. Strong interpersonal skills for collaboration

Looking for your next role in medicinal chemistry?

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