How did you get interested in Medicinal Chemistry?

My interest was first for chemistry and its impact on living systems, which dates from my high school days. Even so at the time I did not know what job would be the most suited for combining chemistry and biology. During my first days at university, I felt in love with organic chemistry, it sounded like making molecule was a lot like assembling a Lego set. From then I knew I wanted to work in this field and during my undergrade I was fortunate to do a 1-year internship at Infinity Pharmaceuticals in Cambridge, MA. This placement reinforced my conviction that medicinal chemist was the job I wanted to do.

Where and when did you obtain your PhD & Postdoc diploma?

I got my PhD from the University of Nottingham in 2015. I started grad school in Edinburgh and after 1 year my PhD advisor, Hon Wai Lam moved the group to Nottingham. I focused on developing novel enantioselective conjugate-additions using transition-metal as well as organocatalyst. Overall, my time as a grad student was a very good training for a future job as a medicinal chemist, as it gave me a good skillset for organic synthesis.

I did my postdoc in the lab of Barbara Imperiali at MIT. I focused on the development of inhibitors and probes applied to the study of the glycosylation pathways of Gram-Negative organisms. This was a completely different environment than my PhD lab and it served me very well to become a medicinal chemist because it prepared me for the cross-functional interactions that a medicinal chemist encounters every day. 

What are your current research interests?

I love working on precision oncology programs. It’s a field which has such a strong impact on patients.
I am also very interested in the integration of technology within the drug discovery process, from target identification, screening, hit validation all the way to clinical trial.

How would you explain what your research area is to non-scientists?

One of my favourite metaphors to describe the job of medicinal chemist is to compare to building a Lego set which needs to impact the biology of a disease. My wife is an interior designer so I also use the analogy of kitchen cabinets design to describe it. If the cabinet is the drug and an apartment building being the body. You must build a cabinet that fits for one apartment only and it has to be built and assembled outside, then it has to make its way to the proper apartment. 

What do you like best about your work?

First I like the finality of our work, trying to find new treatment for patients is such a strong motivation. On a daily basis I like the high pace and the generation of large data set. Trying to solve problems with so many variables using chemistry really keeps me on my toes, so I never get bored. I feel very lucky to be able to combine work and passion, trying to solve those problems is very exciting and stimulating.

What kind of tasks does your work involve?

I focus on the late-stage optimization of lead molecules (lead optimisation). This involves design of new compounds within the chemistry team (synthetic, medicinal, and computational chemists), synthesis at the bench, communication with our CRO partner in Asia, internal communication with the project team and the rest of the company, analysing data, triaging compounds into the different assays, rinse and repeat.

What kind of skills does your work require?

As a chemist, good synthetic skills and the ability to recognize what route/late-stage analogues will be necessary to rapidly expand SAR.As a scientist in general, enthusiasm about the results generated, need to comprehend and integrate a large amount of data (potency, ADME,PK, PD, efficacy…) in order to generate the next round of compounds design.To do it efficiently, communication within a large team is key.

What do you consider your greatest achievement in your scientific career?

Of the one I can talk about; I would say being able to successfully carry out my PhD while having a newborn baby.

Which of your papers are you most proud of and why?

I am going to pick a paper from my postdoc, not that the science is the most novel, but it was a time when I was having issues synthesizing nucleoside analogues. In order to get the project done I had to get out of my comfort zone (thanks to my co-worker Silvano Sanchini for pushing me) and learn and develop a solid phase synthesis which allowed us to make a series of uridine analogues. I also had to learn to express and purify enzymes as well as run enzymatic assays. All those skills really help me now in my interactions with my co-workers from different scientific backgrounds. 
10.1021/acschembio.8b00477

What are the features of a successful PhD student or postdoc?

To be passionate and driven. Talking from my own experience it can sometimes feel lonely and draining, especially when you are facing challenges and you struggle to see the light at the end of the tunnel. Being deeply passionate about your science and driven, knowing why you are going through it and where you want to go afterwards really helps.

How would you describe yourself as a supervisor?

I had the chance to mentor undergrad and master students during both my PhD and postdoc. I love to share my passion for science and to get others involved and be able to express and try their own ideas.

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

Thankfully I haven’t had anything such as an explosion, but I had a small fire once. I was heating a large flask in an oil bath, at around 200 °C (melting urea in order to use it as solvent/reagent), the oil expanded, started to overflow, and I decided to clean the surrounding of the stir plate with some hexane…of course, some got underneath the stirrer plate and caught on fire… 

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

Particular recommendation from blog: In the Pipeline: https://www.science.org/blogs/pipeline

Drughunter: https://drughunter.com/

Have you experienced any unfair situations during your scientific career?

I have been fortunate to not experience many unfair situations during my career. But working in a chemistry lab it’s hard to ignore that chemistry overall lacks diversity. I am hopeful that things are changing for the better. I am involved and I am seeing more initiatives which focus on helping people from different backgrounds to access positions in our department.

Which field of medicinal chemistry do you consider the most promising for the future

I am surely biased but integrating the latest technological progress to shorten cycle time will keep impacting more and more medicinal chemistry in the years to come.
I also thing that new modalities such as molecular glue and PROTAC will be part of the next generation of small molecules as a new efficient tool in the medicinal chemist tool kit.

What advice would you give to someone who wants to know more about your field? 

Reach out to couple of medicinal chemists and get to know the field by chatting with them. If possible, try to find a program that will give you the opportunity for placements within medicinal chemistry departments.

What would you like to ask from other medicinal chemists?

How they prioritize SAR and decide when to keep pushing or abandon a series.
Also, how they balance “strictly rational” design vs empirical libraries.

What would you expect to be the next major breakthrough in medicinal chemistry?

A good maturation of the newest screening methodologies which would contribute to the delivery of high-quality hits. One key aspect is to generate lots of high-quality data which can then be combined with machine learning models in order to deliver superior hits exhibiting good parameters (LLE, selectivity…).