TPD & Induced Proximity – Reflections on Recent Learnings

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It’s more than two decades since targeted protein degradation (TPD) and induced proximity was identified as a new modality. Since then it’s clear that TPD can potentially address proteins that are otherwise challenging to target with traditional small molecules. 

With a number of drugs entering clinical trials TPD shows every sign of going from strength-to-strength. Therefore, it’s vital that drug discovery research partners invest in their scientists’ continuing professional development in this area.

Recently, Charnwood Discovery welcomed Dr Ian Churcher for a series of lectures on Contemporary Targeted Protein Degradation and Induced Proximity.

Reflections on Targeted Protein Degradation & Induced Proximity

Here colleagues from departments across the company reflect on their experience of the training and the benefits.

The first session introduced TPD concepts covering topics such as mechanism of ternary complex, kinetic aspects and degradation assays. Sean Smith, Senior Research Scientist in our Discovery Chemistry department observed:

“Having worked on some chemistry projects involving PROTAC molecules in the past, it was always something that I felt was difficult to understand without extensive experience in the field. However, I have found that Ian’s course has been a fantastic resource for improving understanding. 

Some of the specific nuances relating to how PROTACs should be thought about and optimized when compared to traditional small molecule programs has been enlightening. There are very few resources where all of this knowledge is documented in one place, in such a user-friendly way as this course. 

The use of very recent examples to back up observations has been a great addition as well. This has enhanced my knowledge of the field significantly. A massive thank you to Ian for his compilation and delivery of all of his expertise in the field!”

Building Knowledge of PROTAC Molecules

The course moved on to medicinal chemistry optimization and DMPK. Rachel Doidge, Senior Bioscience Research Scientist has many years of PROTAC experience but highlights how the training expanded on this:

“My previous involvement in PROTAC projects has all been from a purely biological screening perspective. Ian was fantastic at explaining the medicinal chemistry behind drug design, making it interesting and accessible to a wide audience. 

He really focused on the quirks and nuances of PROTAC molecules which has built up my knowledge of PROTAC screening extensively.

 The interactive session of the course was excellent, bringing together the entire mutil-disciplinary team at Charnwood. I would like to thank Ian for his knowledge, warmth and all the work he must have put into developing this course.”

Ryan Mordue, Senior Bioscience Research Scientist, who has PROTAC and molecular glue experience, concurred with this assessment: 

“Having been involved in projects based on TPD using PROTAC and molecular glue molecules, this course really bolstered my foundational knowledge in this new and exciting field of discovery. 

Ian was fantastic at aiming key messages of PROTAC discovery to our multidisciplinary team, with the content enjoyed by all. The up-to-date course resources available to us to reflect on for future projects was a bonus. 

The final session workshop was also one of the best I’ve attended. It really enabled us to use our specific skill sets in a collaborative manner. A big thank you to Ian for the excellent delivery of the course and sharing his wealth of knowledge with us.”

Principal Research Scientist, Lucy Burton observed the following, this time from an ADME / DMPK perspective:

“Ian’s course on PROTACs was excellent and I am grateful for the opportunity to learn from someone so knowledgeable. Our understanding of the best ways of working with these newer modalities is continuously evolving and Ian’s course has reinforced the differences between PROTACs and small molecules.


It was great to see that our approach for handling past projects was consistent with the latest industry-wide learnings on the best way forward. We’ve also picked up some tips and tricks to apply in the future.

Putting TPD Theory into Practice

The final session challenged colleagues from Bioscience, ADME/DMPK and Chemistry to put theory into practice. They were tasked with delivering an advanced lead PROTAC for cancer target JAIK1 – all within 90 minutes! With every team performing well there was an equitable awarding of the prize to every team.

Craig Avery, Head of Medicinal Chemistry, summarized the feelings of those who attended with his reflections on the program: 

 

“Having recently had the pleasure of attending Ian Churcher’s TPD course I can attest it’s a most comprehensive and thorough course. It details both the theoretical and practical aspects of TPD drug discovery.

Particularly important beyond the content is Ian’s insight into strategy and how to practically prosecute these types of projects. He’s excellent at bringing his expertise to life for the delegates.

The content was bang up to date with Ian adding in several details from primary literature released the week before one session! Ian is evidently an expert in the field but crucially has the skill to make complex concepts understandable. He is an excellent teacher of scientific material.

The course comes with my highest recommendation and working with Ian to plan the delivery at Charnwood was easy as he is a pleasure to work with.” 

Find Out More

Now armed with the latest in TPD knowledge and strategies our expert multidisciplinary teams are excited to apply this to current and future client projects.

Find out more about our TPD, PROTACs and molecular glue capabilities and services or contact us if you have a specific question or project in mind.

You can also contact Dr Ian Churcher to find out more about the training he delivers here.