Medicinal chemistry CROs and computational chemistry

What is the situation in small and medium Contract Research Organizations (CRO) with a deep expertise in medicinal chemistry?  Some of these CROs have already built computational chemistry efforts in-house or have established collaborations with Computer-Aided Drug Design (CADD) service providers, while some are still reluctant to explore this field.  The main reason is unfamiliarity, which often raises two key questions:

• What are the benefits of adding computational chemistry to a drug discovery project?
• Will computational chemistry over-take medicinal chemistry?

There are multiple benefits to consider:

• Computational chemistry can be used to move High-Throughput Screening (HTS) assays from a brute force approach to guided experiments, reducing HTS costs by up to 1,500X as shown by ex-Pharmacia (now Pfizer) [3].
• Synthesis can also be sped up by allowing medicinal and organic chemists to concentrate on fewer compounds [4] since in-silico models have shown successful use in qualifying hits from HTS [5].
• CADD tools allow fast and inexpensive access to different virtual libraries that increase the chances of exploring a wider chemical space.

All the aforementioned examples are translated into the design and optimization of more robust leads.

The answer to the second question is an outright “no”: computational chemistry cannot substitute medicinal chemistry know-how. Computational chemistry provides more insights into ligand-target interactions and this information is very useful for medicinal chemists in the creative process of lead design and optimization.

Collaboration models

There are several ways in which a medicinal chemistry CRO can use CADD as complementary technology: It may either build such an effort in-house or establish external collaborations with a preferred partner.

Alternatively, it may establish relationships with several partners on a per-project basis. In case of external partners, several factors need to be considered such as the technology, area of expertise and know-how, costs, trust, flexibility and geographical influence.

In summary, computational chemistry is used as a complementary technology to reduce the costs and increase the efficiency of target-to-hit, hit-to-lead and lead optimization drug discovery stages. In the new collaborative and fragmented drug discovery ecosystem [6], new opportunities arise to reduce the gap between extremely specialized organizations and consequently improve efficiency in R&D.

Have an open discussion with us!

To find out how Pharmacelera can help you to complement your technology with CADD, contact us for an open discussion.

References

[1] G. Sliwoski, S. Kothiwale, J. Meiler, E. Lowe, “Computational Methods in Drug discovery”, Pharmacological Reviews, January 2014
[2] T.J. Ritchie, I.M. McLay, “Should medicinal chemists do molecular modelling?”, feature in Drug Discovery Today, January 2012

[6] S. Mignani, S. Huber, H. Tomás, J. Rodrigues, J-P. Majoral, “Why and How Have Drug Discovery Strategies Changed? What are the New Mindsets?”, Drug Discovery Today, February 2016

The post Are medicinal chemistry CRO complementing their technology with computational chemistry? appeared first on Pharmacelera | Pushing the limits of computational chemistry.