Image credit: Orhan Turan, iStock by Getti Images.
Drug discovery is a long and challenging process, which may take up to fifteen years of experimentation and clinical trials, and several billion dollars in various expenses to bring a successful drug to patients. The process can be roughly divided into three stages: 1) biology research and early drug discovery; 2) preclinical drug development; and 3) clinical trials.
In order to start a drug discovery program, at the first stage, scientists study biological processes to come up with proper understanding of the underlying causes of a particular disease. Once drivers of the disease are known, scientists can select specific biological targets -- typically proteins involved in a disease-causing biological process.
When a suitable target is identified, the actual drug discovery work begins: researchers try to find appropriate chemical compounds that would bind to a biological target such that a desired modulating effect is achieved, for instance, the protein inhibition. In order to find such unique “keys” to biological “locks”, the scientists either screen blindly millions of available chemical compounds against the protein of their interest in their biological assays, or computationally identify most promising compounds and then test them.
Either way, one of the key bottlenecks of this process is the need for chemical synthesis of the enormous quantities of different chemical compounds, oftentimes, structurally sophisticated and hardly obtainable in the lab. When initial sets of relevant biologically active molecules (so called “hits”) are selected from many thousands, sometimes millions, of existing drug-like molecules, an additional chemical challenge is to optimize them towards better pharmacological properties, stability, solubility, etc. This, in turn, also requires a lot of chemical expertise, technological resources, and unique chemical compounds, readily available for research work.
In order to manage those “chemical needs'' of the drug discovery process, drug development companies and labs from around the globe have increasingly relied on a handful of Ukrainian firms, in particular, Enamine, the largest of them. This reliance has grown over the last three decades, as a result of Enamine’s outstanding chemical offering and sophistication of available products, not easily found elsewhere. The Enamine’s chemical capabilities, including the world’s largest stock of building blocks and screening compounds, have become an important resource for thousands of drug discovery and biotech companies, including leading global pharmaceutical brands, as well as hundreds of universities and drug discovery centers around the globe.
The war, new realm, new worries
The unprovoked Russian aggression in Ukraine, and the full scale war that the Russian Federation started on February 24, 2022, not only led to a humanitarian crisis in Ukraine, with a mounting death toll among civilian Ukrainian population, but also caused major disruptions in business operations, including those of Enamine and other Ukrainian chemical suppliers. As a result, numerous early stage drug discovery programs around the globe faced complications and delays.
During the first days of war, Endpoints News interviewed a number of drug discovery executives and opinion leaders and found that the concern was growing in drug discovery and biotech communities as to how the situation in Ukraine would be impacting the industry.
“Pretty much everybody orders from them at one time or another,” commented Derek Lowe, a well-known voice in the community of medicinal chemists, for Endpoints News.
“So there is definitely a level of wariness here,” commented Michael Gilman, CEO of Arrakis, a Waltham, Massachusetts-based biotech developing small molecules that target RNA.
Donna Romero, head of chemistry at ROME Therapeutics, an ARCH-backed biotech in cancer and autoimmune diseases, told Endpoints News: “Ukraine was able to develop this really world-class business that impacts drug discovery globally.”
In 2018 Duncan B Judd of the consulting firm Awridian in collaboration with researchers from Ukraine, Latvia, and France conducted a survey of the market for high-throughput screening compounds used in drug discovery (Drug Discov. Today 2019, DOI: 10.1016/j.drudis.2018.10.016). They concluded that companies in Ukraine and Russia, with the largest of them being Enamine, supply around 80% of the world’s screening compounds for high-throughput screening programs. “I’m not sure people realize the scale of the problem,” Duncan B Judd tells C&EN commenting on possible consequences of the invasion of Ukraine “It’s going to make a big impact.”
The unexpectedly tangible role, which Ukrainian chemical suppliers, like Enamine, play in the global pharmaceutical research, hit headlines of leading biopharmaceutical and mainstream media outlets, including Endpoints News, Statnews, Fierce Pharma, C&EN, BioCentury, Chemistry World, The Wall Street Journal, Bloomberg, and others.
With this post, we are going to establish a historical track about this difficult and turbulent period for Enamine, and Ukrainian scientific community in general: we will be regularly updating a running list of media publications featuring the company during the ongoing war (the list of articles is at the end of this post).
Not only chemicals…
It appears that not only early drug discovery programs are going to be affected by the war in Ukraine -- according to a prestigious British magazine WIRED, Ukraine had a reputation as a hub for clinical trials… until Russia invaded. The country possesses a sizable, capable medical and research workforce with a reputation for delivering reliable data, while recruitment of patients in Ukraine is believed to be easier, compared to some Western countries. The Ukrainian government recently overhauled its medical system to introduce a national digital records system, adding to Ukraine’s attractiveness as a global clinical trials destination.
At the end of February 2022, Clinicaltrials.gov listed as many as 635 ongoing interventional trials in various recruiting and enrollment stages with at least one study site in Ukraine including studies in the recruiting stage. Another resource, GlobalClinicalTrials, estimates a smaller but still considerable number of clinical trials in Ukraine -- around 500 studies every year. Not only small and medium biotechs, but also big pharma companies are among trial sponsors, meaning the negative effect of war on pharmaceutical research will be felt across the industry and, potentially, long into the future.
While Enamine is not directly involved in the market of clinical trials, the interruptions in the supply of Enamine research chemicals for the drug discovery community can also become an indirect negative factor impacting future clinical trials: after all, clinical candidates are developed initially based on drug-like molecules of a kind produced by companies like Enamine.
Resisting the aggressor
We, at Enamine, have united to resist the Russian invasion the way we can. We have recently launched Enamine Charity Fund to help acquire non-lethal military aid to enhance the defense of Ukraine, provide medical supplies to the hospitals, provide sponsorship for science and education in Ukraine, and help our employees scattered by war across Ukraine and abroad. If you want to contribute to ending the war in Ukraine soon, please, consider donating (bank details in various currencies are provided).
We would like to also thank all those who already contributed financial support to our Charity Fund. We will be publishing regular updates on the Fund’s activity and related stories in this blog’s dedicated channel: Enamine Charity Fund -- please, refer to it for further information and future status updates.
A running list of media coverage: Enamine and its scientists during the war in Ukraine