New research uses AlphaFold, an artificial intelligence (AI)-powered protein structure database, to accelerate the design and synthesis of a drug to treat hepatocellular carcinoma (HCC), the most common type of primary liver cancer. It is the first successful application of AlphaFold to hit identification process in drug discovery. This study by an international team of researchers, published last week in Chemical Science, is led by the University of Toronto’s Acceleration Consortium director Alán Aspuru-Guzik, Chemistry Nobel laureate Michael Levitt, and Insilico Medicine founder and CEO Alex Zhavoronkov.
AI is revolutionizing drug discovery and development. In 2022, the AlphaFold computer program, developed by Alphabet’s DeepMind, predicted protein structures for the whole human genome––a remarkable breakthrough in both AI applications and structural biology. This free AI-powered database is helping scientists predict the structure of millions of unknown proteins, which is key to accelerating the development of new medicines to treat disease and beyond.
In this new Chemical Science paper, AlphaFold was successfully applied to an end-to-end AI-powered drug discovery platform called Pharma.AI, including a biocomputational engine, PandaOmics, and a generative chemistry engine, Chemistry42. Researchers discovered a novel target for HCC – a previously undiscovered treatment pathway – and developed a novel hitmolecule – a molecule that could bind to that target – without the aid of an experimentally determined structure. This was accomplished in just 30 days from target selection and after only synthesizing 7 compounds. In a second round of AI-powered compound generation, researchers discovered a more potent hit molecule.
“While the world was fascinated with advances in generative AI in art and language, our generative AI algorithms managed to design potent inhibitors of a target with an AlphaFold-derived structure,” said Alex Zhavoronkov, founder and CEO of Insilico Medicine.
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“AlphaFold broke new scientific ground in predicting the structure of all proteins in the human body,” said Feng Ren, co-author, Chief Scientific Officer and co-CEO of Insilico Medicine. “At Insilico Medicine, we saw that as an incredible opportunity to take these structures and apply them to our end-to-end AI platform in order to generate novel therapeutics to tackle diseases with high unmet need. This paper is an important first step in that direction.”
Without AI, scientists must rely on conventional trial and error methods of chemistry that are slow, expensive and limit the scope of their exploration. As COVID-19 has demonstrated, the speedy development of new drugs or new formulations of existing ones is needed and increasingly expected by the public. AI has the potential to deliver this speed by transforming materials and molecular discovery, as it has done with just about every branch of science and engineering over the last decade.
“This paper is further evidence of the capacity for AI to transform the drug discovery process with enhanced speed, efficiency, and accuracy,” said Michael Levitt, Nobel Prize winner in Chemistry, Robert W. and Vivian K. Cahill Professor of Cancer Research and Professor of Computer Science, Stanford University. “Bringing together the predictive power of AlphaFold and the target and drug design power of Insilico Medicine’s Pharma.AI platform, it’s possible to imagine that we’re on the cusp of a new era of AI-powered drug discovery.”
“What this paper demonstrates is that for healthcare, AI developments are more than the sum of their parts,” said Alan Aspuru-Guzik, a professor of chemistry and computer science at the University of Toronto and the Canada 150 Research Chair in Theoretical and Quantum Chemistry. “If one uses a generative model targeting an AI-derived protein, one can substantially expand the range of diseases that we can target. If one adds self-driving labs to the mix, we will be in uncharted territory. Stay tuned!”
Both Insilico Medicine and the Acceleration Consortium, a University of Toronto initiative that Aspuru-Guzik directs, are working actively to develop self-driving laboratories, an emerging technology that combines AI, automation and advanced computing to accelerate materials and molecular discovery. Accessible tools and data will help more scientists enter the field of AI for science, in turn helping to drive major progress in this area.
Insilico Medicine is a clinical stage company developing an AI-based end-to-end integrated pipeline for drug discovery and design, with the first AI-discovered and AI-designed drug, for idiopathic pulmonary fibrosis, to advance to positive Phase 1 topline results, and 30 other drugs in its pipeline, for cancer, fibrosis, immunity, central nervous system diseases, and aging-related diseases. Both Aspuru-Guzik and Levitt are advisors to Insilico. The Acceleration Consortium is a global community of academia, industry, and government working together to accelerate the discovery of new molecules and materials needed for a sustainable future.
Reference: Ren F, Ding X, Zheng M, et al. AlphaFold accelerates artificial intelligence powered drug discovery: efficient discovery of a novel CDK20 small molecule inhibitor. Chem Sci. 2023. doi: 10.1039/D2SC05709C
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NAIROBI, Kenya (AP) — The body of Ugandan Olympic athlete Rebecca Cheptegei — who died after being set on fire by her partner in Kenya — was received Friday by family and anti-femicide crusaders, ahead of her burial a day later.
Cheptegei’s family met with dozens of activists Friday who had marched to the Moi Teaching and Referral Hospital’s morgue in the western city of Eldoret while chanting anti-femicide slogans.
She is the fourth female athlete to have been killed by her partner in Kenya in yet another case of gender-based violence in recent years.
Viola Cheptoo, the founder of Tirop Angels – an organization that was formed in honor of athlete Agnes Tirop, who was stabbed to death in 2021, said stakeholders need to ensure this is the last death of an athlete due to gender-based violence.
“We are here to say that enough is enough, we are tired of burying our sisters due to GBV,” she said.
It was a somber mood at the morgue as athletes and family members viewed Cheptegei’s body which sustained 80% of burns after she was doused with gasoline by her partner Dickson Ndiema. Ndiema sustained 30% burns on his body and later succumbed.
Ndiema and Cheptegei were said to have quarreled over a piece of land that the athlete bought in Kenya, according to a report filed by the local chief.
Cheptegei competed in the women’s marathon at the Paris Olympics less than a month before the attack. She finished in 44th place.
Cheptegei’s father, Joseph, said that the body will make a brief stop at their home in the Endebess area before proceeding to Bukwo in eastern Uganda for a night vigil and burial on Saturday.
“We are in the final part of giving my daughter the last respect,” a visibly distraught Joseph said.
He told reporters last week that Ndiema was stalking and threatening Cheptegei and the family had informed police.
Four in 10 women or an estimated 41% of dating or married Kenyan women have experienced physical or sexual violence perpetrated by their current or most recent partner, according to the Kenya Demographic and Health Survey 2022.
TEL AVIV, Israel (AP) — A rare Bronze-Era jar accidentally smashed by a 4-year-old visiting a museum was back on display Wednesday after restoration experts were able to carefully piece the artifact back together.
Last month, a family from northern Israel was visiting the museum when their youngest son tipped over the jar, which smashed into pieces.
Alex Geller, the boy’s father, said his son — the youngest of three — is exceptionally curious, and that the moment he heard the crash, “please let that not be my child” was the first thought that raced through his head.
The jar has been on display at the Hecht Museum in Haifa for 35 years. It was one of the only containers of its size and from that period still complete when it was discovered.
The Bronze Age jar is one of many artifacts exhibited out in the open, part of the Hecht Museum’s vision of letting visitors explore history without glass barriers, said Inbal Rivlin, the director of the museum, which is associated with Haifa University in northern Israel.
It was likely used to hold wine or oil, and dates back to between 2200 and 1500 B.C.
Rivlin and the museum decided to turn the moment, which captured international attention, into a teaching moment, inviting the Geller family back for a special visit and hands-on activity to illustrate the restoration process.
Rivlin added that the incident provided a welcome distraction from the ongoing war in Gaza. “Well, he’s just a kid. So I think that somehow it touches the heart of the people in Israel and around the world,“ said Rivlin.
Roee Shafir, a restoration expert at the museum, said the repairs would be fairly simple, as the pieces were from a single, complete jar. Archaeologists often face the more daunting task of sifting through piles of shards from multiple objects and trying to piece them together.
Experts used 3D technology, hi-resolution videos, and special glue to painstakingly reconstruct the large jar.
Less than two weeks after it broke, the jar went back on display at the museum. The gluing process left small hairline cracks, and a few pieces are missing, but the jar’s impressive size remains.
The only noticeable difference in the exhibit was a new sign reading “please don’t touch.”
VICTORIA – The British Columbia government is partnering with a bear welfare group to reduce the number of bears being euthanized in the province.
Nicholas Scapillati, executive director of Grizzly Bear Foundation, said Monday that it comes after months-long discussions with the province on how to protect bears, with the goal to give the animals a “better and second chance at life in the wild.”
Scapillati said what’s exciting about the project is that the government is open to working with outside experts and the public.
“So, they’ll be working through Indigenous knowledge and scientific understanding, bringing in the latest techniques and training expertise from leading experts,” he said in an interview.
B.C. government data show conservation officers destroyed 603 black bears and 23 grizzly bears in 2023, while 154 black bears were killed by officers in the first six months of this year.
Scapillati said the group will publish a report with recommendations by next spring, while an independent oversight committee will be set up to review all bear encounters with conservation officers to provide advice to the government.
Environment Minister George Heyman said in a statement that they are looking for new ways to ensure conservation officers “have the trust of the communities they serve,” and the panel will make recommendations to enhance officer training and improve policies.
Lesley Fox, with the wildlife protection group The Fur-Bearers, said they’ve been calling for such a committee for decades.
“This move demonstrates the government is listening,” said Fox. “I suspect, because of the impending election, their listening skills are potentially a little sharper than they normally are.”
Fox said the partnership came from “a place of long frustration” as provincial conservation officers kill more than 500 black bears every year on average, and the public is “no longer tolerating this kind of approach.”
“I think that the conservation officer service and the B.C. government are aware they need to change, and certainly the public has been asking for it,” said Fox.
Fox said there’s a lot of optimism about the new partnership, but, as with any government, there will likely be a lot of red tape to get through.
“I think speed is going to be important, whether or not the committee has the ability to make change and make change relatively quickly without having to study an issue to death, ” said Fox.
This report by The Canadian Press was first published Sept. 9, 2024.
