In Ukraine, he was creating the building blocks for drug developers

IIt was only last month, when the Covid-19 situation had calmed down in Kyiv, that Ivan Kondratov was able to return to his office for a few days a week. He has managed a multitude of medicinal chemistry projects, including the construction of “target libraries” for clients, primarily large biopharmaceutical companies around the world.

His employer, Enamine, had become a mainstay of global drug development, his Rolodex of customers growing steadily as well as his catalog of chemical compounds for drugmakers to test to create potential treatments.

But on February 24, that all came to a halt when Kondratov and hundreds of thousands of other Ukrainians were awakened by the sound of explosions. And everything has changed for chemists and scientists.

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“The situation developed very, very quickly,” Kondratov told STAT, speaking by phone from a town in northwestern Ukraine where he had taken refuge. “Thursday morning they started bombing and attacking, and many families, many of our colleagues just took their families and walked out, left.” Suddenly, reading the latest published research, figuring out what chemicals his team could synthesize, didn’t matter. “It was my routine. And now I don’t even think about it,” he said.

Enamine, headquartered in a former Soviet chemical factory on the left bank of the Dnieper that divides Kiev, is a major supplier of chemicals used in pharmaceutical laboratories from Boston to Tokyo. He was instrumental in Covid Moonshot’s efforts to create a pill for the disease.

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It’s one of many companies that have pioneered a new industry over the past three decades, said longtime drug discovery researcher Derek Lowe. The Ukrainian chemical world was born out of the fall of the USSR by capitalizing on a reserve of “strange” compounds that had not been explored in countries like the United States due to the divide between Soviet chemical research and the Western world.

Enamine, along with two other Ukrainian companies, Otava Chemicals and Life Chemicals, filled a gap in the market, offering “interesting” off-the-shelf building blocks that drug developers could easily incorporate into their work, and creating custom libraries of these chemical treats for businesses. “It’s really changed the way medicinal chemists work,” said Lowe, who works at Novartis (but didn’t speak on behalf of the company).

Instead of having to do this work in-house, companies could outsource the work to Ukraine, making it more efficient and affordable. This activity has since become a crucial part of drug development worldwide. “I’m pretty sure that most of the drug discovery projects that have led to the development of drug candidates and drugs over the past five years, more or less, have dealt with our products and services,” said Kondratov. Perhaps the company’s most impressive offering is a catalog of 20 billion synthetic compounds that companies can digitally view and order a la carte.

The invasion threatens to derail this and other preliminary research, as many companies rely on Ukrainian chemistry. “Now suddenly there’s a bunch of reagents that we can’t get anymore,” Lowe said. Across the industry, chemists have to make up for the supply problem, whether developing small molecules in-house or finding another company to supply them.

The average person doesn’t feel that pressure, but in the long run, “it would definitely put a dent in the drug pipeline,” Lowe said. Warehouses full of chemical building blocks could be destroyed, libraries never released. “All of this is just blown away by an event like this. And that unfortunately shows you the fragility of something like science, research and intellectual pursuits,” he said. “Because none of these resist cluster bombs very well.”

Enamine’s operations in Kyiv came to a halt on February 24. Its staff of 1,000 is dispersed, with each employee having to make the decision to flee or stay, knowing that the threat could continue indefinitely.

That Thursday morning, after the explosions woke him around 6 a.m., Kondratov tried to cut through the mess of online rumors and misinformation, and came to this: He had to leave Kyiv. “I understood that it was really necessary to transfer my family, to take my family as far as possible,” he said.

Along with a few other families, Kondratov asked his children, ages 10 and 6, to put away their clothes, and together with a few other families they loaded up their vehicles and set off on the long journey west. Along the way, they encountered traffic jams and “huge, huge, huge queues” at petrol stations that limited each car to 30 liters and then 20.

He was lucky. He left central Ukraine ahead of seemingly indiscriminate attacks by Russian troops on residential areas. “Now I see how my children’s classmates, many of them spent their time in the shelters, sometimes all night,” he said. His parents took one of the last flights out of the country the day before the invasion began and traveled to Paris to stay with Kondratov’s sister.

But Kondratov didn’t feel lucky after 12 hours of driving, when he dropped off his wife and children in Poland and traveled to Volodymyr, a town in northwestern Ukraine, to stay there indefinitely. . Due to his age, he cannot leave Ukraine in case he needs to defend the country. Many of his friends did the same – first tried to save their families, then found lodgings in villages, towns and cities in western Ukraine. They volunteer to help in any way they can. For Kondratov, that meant helping local police patrol the streets.

Some men he knows have returned to Kiev to join the fight. Other friends couldn’t leave at all. In towns like Chernihiv — not far from Kiev, in the north of the country near Belarus — which was quickly surrounded by Russian troops, it is impossible to get out.

“I just got messages from them saying they’re sitting in the shelters, sitting underground, listening to the bombs, and it’s terrible,” Kondratov said. STAT spoke to him ahead of Friday reports of explosions in Lutsk, about 80 km east of Volodymyr.

War is no stranger to most Ukrainians. The conflict with Russia in the country’s east has simmered in the background of life for years, said Kondratov, who was raised by chemist parents about 10 kilometers from that combat zone. He had seen this conflict worsen and, over the past few years, subside. And he knew, as early as December, that Russian troops gathering on the border with Ukraine meant there was a high risk of invasion.

But the feeling of war, the lived reality of what it does to one’s mind, to one’s priorities, to be attacked, it’s surreal.

“It’s hard to explain,” Kondratov said. “I see so many things I should or can do, and I understand that I absolutely don’t have the time or the resources to do them all. There are things I should do to save our people. There are actions I should take to save at least some of our customers because obviously we understand that as long as this war continues we will start losing our customers…. We have to make a lot of tough decisions right now.

Back in Kyiv, those who remained helped clear flammable materials from the Enamine campus labs, just in case the buildings were bombed. The company has announced plans to relocate some of its 700 chemists to Riga, Latvia, where Enamine stocks compounds for customers in Europe. The now-closed Kyiv campus housed most of the company’s work, but an Enamine facility in New Jersey allowed some activities to continue.

From left to right: Veronika Shoba, Basudeb Mondal, Uttam Dhawa, Arghya Deb, Praveen Tiwari, Santosh Chaudhary, Amedeo Vetere and Prashant Singh. Researchers from Harvard’s Broad Institute and MIT hold a Ukrainian flag in the lab Friday, March 11, two weeks after Russian troops began their invasion. Scientist Veronika Shoba (far left) grew up in Lviv, Ukraine, and worries about how the invasion threatens to derail the country’s important chemical work. Courtesy of Veronika Shoba

This is how Veronika Shoba received a package from Enamine on February 25, a day after the invasion. Shoba, a scientist at the Broad Institute of MIT and Harvard, was surprised when she received a shipment of 500 milligrams of N-Benzyl-N-Methylaminosulfonamide, a chemical that Shoba’s lab is using to create a potential new anti-cancer therapy.

A Belarusian who grew up in the western Ukrainian city of Lviv, Shoba is all too familiar with the situation facing her country. Every morning before work, she spends several hours reading the news, messaging friends and family in Ukraine to check on their well-being, and searching social media for people she can help. connect with resources, even though they are thousands of miles away.

“I keep thinking, ‘Who else could be there? Who else could I help? ” Shoba told STAT. “Even with people I’ve had huge fights with before and thought I’d never talk to that person, we’re friends, back, because it doesn’t matter.”

Then she goes to work at the Broad, where she informs her colleagues of the situation. In her spare time, Shoba investigates links between Russian oligarchs and institutions such as Harvard, and she writes letters appealing to senators and other powerful people, hoping someone might have the clout to help Ukraine. to defend its airspace. Life is hectic, consumed by invasion. “I don’t think I’m doing a lot of work,” she said, noting the Broad had been supportive.

Shoba, like many Ukrainians living abroad, is overwhelmed by the shocking toll – the scale and depth of the damage being done. With death and destruction of property come a universe of a million small losses. As a child interested in science, Shoba participated in the International Science Olympiads in the spring, preparing months in advance. She cries when she thinks of the talented kids who worked so hard for this year’s competition, who won’t have that experience. The university where they were preparing was bombed, destroyed.

“I’m shocked. But it also made me think a lot about previous wars, which weren’t in my home country, but which I didn’t pay attention to,” she said. it wasn’t about me, not my family and friends, i was reading about it in the news, i just felt sad but i don’t think i fully understood the tragedy behind the war…c is very abstract until you are a part of it.