Early on in my life, the transformative impact anti-histamine and asthma medicines had on my life awakened a deep curiosity in how medicines work. Eventually I found myself working on teams attempting to design those medicines, most recently within Pfizer’s Medicine Design organization.
Discovering and inventing medicines to transform patients’ lives is our group’s mission, and we aim for this across disease areas such as Oncology, Inflammation and Immunology, Rare Diseases and Internal Medicine (cardiovascular and metabolic diseases, Non-Alcoholic SteatoHepatitis (NASH) etc..). To do this well, many scientists from different disciplines come together to design small molecule compounds with carefully balanced physiochemical and structural properties to ensure they bind to and modulate the biological target selected, can be dosed effectively to reach the required target and survive in the body long enough to have the desired efficacious effect …and do all of this safely (figure 1). Being able to apply our scientific disciplines, as described above, to identify new medicines is such an exciting opportunity – utilizing the science we love to make a difference to patients around the world.
Figure 1: Charlotte Allerton emphasizes that most inventions and breakthroughs come from working in diverse teams of colleagues. Here she is discussing project progress with a colleague in the Pfizer laboratories in Groton, CT.
Describe your present position:
I am fortunate enough to lead the Medicine Design organization in Pfizer. Medicine Design includes three primary focus areas:
Medicinal Chemistry, where colleagues across many branches of chemistry (synthetic chemistry, design chemistry, computational chemistry, chemical biology, analytical chemistry etc) come together to identify new chemical matter on which to start drug discovery projects, and then optimize those molecules into potential drug candidates. This involves using approaches such as structure based drug design to identify the optimal ligand for the target protein, while also building in good oral drug properties and synthetic methodology to underpin an expedited path to clinical testing. For example, our team used a novel approach to design for a lung cancer treatment that crosses the blood-brain barrier, while also addressing some of the resistance mutations that can occur in cancer treatment. This is now an approved drug, Lorbrena, which provides a treatment option to some patients with non-small cell lung cancer.
Pharmacokinetics, Dynamics and Metabolism (PDM) where scientists work to determine the Absorption, Distribution, Metabolism and Elimination (AMDE) profiles of drug molecules, in order to understand “what the body does to the drug”, alongside understanding the pharmacology of the drug which dictates “what the drug does to the body”. This includes incorporating an understanding of these processes into the design of potential drug molecules as well as describing these characteristics of drug molecules to the regulators during clinical development, to help underpin a drug approval. For example, in designing a potential treatment for the metabolic disease NASH, Pfizer scientists learned that by targeting the liver directly, they could avoid toxicity issues that were seen with systemic dosing.
Discovery Sciences, which encompasses many of the scientific disciplines that underpin the design of small molecule medicines, such as structural biology, to better understand target protein structures in an effort to enable the efficient design of small molecules to bind to the targets, as well as early primary pharmacology and hit identification screening technologies to form predicted “patient relevant” screen sequences that may assist as a guide for drug design.
We work together across all of these areas, with our disease area experts in biology and clinical, to identify new potential medicines and advance them into clinical trials.
Did you get to your present position because of your background in chemistry and area of specialization or did life experience(s) take you there?
My first position within Pfizer was as a synthetic chemist within Medicinal Chemistry working on high throughput synthesis, a technique we use to make large numbers of diverse compounds to expedite the identification of lead compounds, which often form the starting point for further optimization in early discovery programs. So – having a background in chemistry was certainly important in being offered my first job, but it was the continued growth of my chemistry expertise, as well as drug discovery and development knowledge through exposure to projects and through working with very experienced colleagues that kept me hooked on learning more.
After being involved in a number of drug discovery programs, I became fascinated by the relationship between the physiochemical properties of molecules, and how they interact with drug targets and distribute in the human body. The lipophilicity of molecules is one such important property which has to be carefully balanced in drug design. If it is too high, then the molecule may be insoluble or highly metabolized by the liver which is generally not commensurate with a good oral drug – but if it is too low, then it may not cross cell membranes to reach the biological target or may have oral absorption challenges. This fascination led me to move from the Medicinal Chemistry department to the PDM department, where I could learn more about the ADME processes that guide molecule design as well as deepen my clinical experience. This gave me insight into a broad range of science, from transporters in the human liver to enable us to design liver targeted molecules, to human ADME studies in clinical development which underpin our understanding of “what the body does to a drug molecule” as part of the process of seeking drug approval. After several years, I was given the opportunity to lead the small molecule PDM organization in Pfizer and then subsequently take on leadership of the broader Medicine Design organization bringing together all the critical disciplines in the small molecule drug discovery engine, and in particular the medicinal chemistry discipline where I started.
In which area of chemistry did you specialize?
I joined Pfizer after my undergraduate degree where I had studied physical, inorganic and organic chemistry but specialized in organic chemistry. After a few years of deepening my chemistry expertise within Pfizer, I did a MPhil at the University of Cambridge working on the total synthesis of Elaiophylin with Professor Ian Paterson, which provided a great learning experience in synthetic chemistry problem solving. In addition, having the opportunity to spend time in academic research laboratories, and with different academic groups, proved a stimulating experience in terms of exposure to broader research areas and the intensity of the academic environment.
Do you use chemistry on a daily basis? Describe what you do on a day-to-day basis.
Yes – every single day. Much of my day-to-day work involves meeting with scientists and clinicians to discuss the progress of our drug discovery projects, and to decide which molecules we should progress into clinical development and which we believe do not have the right characteristics to be successful (see figure 2). This involves a lot of chemistry, such as seeking the best synthetic and analytical methodologies in an effort to create diverse molecules in pursuit of the ultimate drug molecule and then to enable scale up to provide enough Active Pharmaceutical Ingredient (API) to support clinical trials. We also assess whether our molecules are binding to the target protein in the most efficient way or whether there are additional interactions we could possibly utilize, and whether the physiochemical properties of our potential drug molecules are optimized to enable a good oral or topical drug molecule. In addition to ensuring we are making progress on our current portfolio of drug discovery projects, we are always looking to the future and seeking new technologies to aid us to be more effective at treating disease, as well as to accelerate drug discovery. I spend time working with many scientists on deciding where to invest, and reviewing many diverse opportunities such as protein degraders to expand drug space, and high throughput reaction optimization to identify ideal reaction conditions more rapidly. In order to do this well, we need to stay on top of the emerging scientific literature as well as the work of biotechnology companies. Chemistry underpins everything we do – and I have many opportunities every day to apply my chemistry knowledge.
Figure 2: Charlotte Allerton explains that meeting with scientists and clinicians to discuss drug discovery projects forms an important part of her work. Here she is reviewing data with colleagues.
Describe the personal skills that have played an essential role in your present position.
All scientists need to be resilient and tenacious to make progress! We have to keep our eye on the ultimate goal, which in our case is to discover new medicines, and keep tackling the scientific challenges that it poses. Picking ourselves up after a failure, taking a step back and working out a new route to the goal is an important skill. And celebrate the successes!
Whether we work in academia or industry, most inventions and breakthroughs come from working in diverse teams of colleagues. Being able to listen to others’ views, advocate for your own, cut through the complexity to a clear plan and build trust through acknowledging the contributions of others are all key skills in achieving scientific success.
Finally – we all have stakeholders – whether it is our professor, the patients we are trying to treat, or our investors! It is important that we communicate effectively to build our stakeholder’s confidence in our research. Contextualizing the work we do to the ultimate goal, while being pithy and engaging, are good skills to work on.
What advice do you have for those who wish to pursue this or some other non-traditional career path?
Studying chemistry is a great starting point to many, many careers – including a rewarding career in the pharmaceutical industry and healthcare research. Start by going deep in your discipline to set a really solid foundation for your career, and then begin to layer on different ways to apply your science and grow your knowledge of drug discovery and development. Whatever career you choose, remember you learn as much from your failures as you do from your successes, and chemistry continues to surprise us every day, so stay humble and ready to learn!
How and where can readers learn more about this type of career?
There are several links included in the descriptions above, that will take you to Get Science articles giving more details on these areas of science and how they apply to drug discovery. There is also a podcast episode that tells more about my career, and several other podcasts that tell the interesting stories of some of my colleague’s careers.
For further information about a career in medicine design, check out these stories:
On the drug discovery and development process overall:
- What it Takes to Discover and Develop a Medicine Get Science Pfizer. (accessed 6/24/29)
- Fujimori, Sachi, Medicine's 2-Way Dance: What a Drug Does to the Body and What the Body Does to the Drug, Get Science, Pfizer, March 23, 2018. (accessed 6/24/19)
- Fujimori, Sachi, Advanced Culture: Making More 'Life-Like' Cellular Models, Get Science, Pfizer, March 23, 2018. (accessed 6/24/19)
On tackling challenges in drug discovery:
- Shin, Paul, Cryo-Electron Microscope Opens Resolution Revolution for Biological Imaging, Get Science, Pfizer, August 14, 2017. (accessed 6/24/19)
- Shin, Paul, Getting a Medicine to the Brain is a Major Challenge in Drug Design: How This Scientist Solved It, Get Science, Pfizer, April 25, 2018. (accessed 6/24/19)
- Unlocking the Secrets of a Protein "Superfamily", Get Science, Pfizer, October 5, 2018. (accessed 6/24/19)
- Shin, Paul, When Cancers Develop Resistance, 'Stealthy' Medicines Can Help, Get Science, Pfizer, March 16, 2018. (accessed 6/24/19)
On career paths:
- Get Science Podcast: A Mind for Design (Charlotte Allerton), Get Science, Pfizer, April 24, 2019. (accessed 6/24/19)
- Get Science Podcast: Doing the Undoable (Megan Robinson), Get Science, Pfizer, December 3, 2018. (accessed 6/24/19)
- Get Science Podcast: Seeing Science With Varied Lenses (Susanna Tse), Get Science, Pfizer, January 2, 2019. (accessed 6/24/19)
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