The institute’s scientists have identified a molecule that irreversibly adheres to a protein that contributes to the development of malignant tumors. Their findings may lead to the creation of a new cancer drug
Most drugs, from paracetamol to cancer drugs, are based on molecules that move in the body, bind to proteins and help prevent or fight diseases. However, the connections between the molecules that are introduced into the body and the proteins last for short periods of time, so their effectiveness may be limited. The laboratory of Dr. Nir London, from the Department of Structural and Chemical Biology at the Weizmann Institute of Science, specializes in the detection of molecules of a special type – those that bind to proteins throughout their lives, lasting from a few hours to several days.
In a new study, researchers from Dr. London’s lab focused on a protein called Pin1, which has been known for years to play a role in the development of various cancers. Able to bind to a protein and disrupt its activity – and from which a drug may be formed – failed.
The researchers speculated that if they found a molecule that would bind to Pin1 irreversibly and disrupt its activity, it might prevent it from supporting the disease in two ways: it would not encourage other proteins that accelerate the tumor and would not inhibit proteins capable of fighting cancer. The study also involved Prof. Nathaniel Gray of the Dana Farber Institute for Cancer Research in Boston and Prof. Con Ping Lou of Harvard Medical School.
To find the right molecule, hundreds of potential candidates were scanned until those capable of binding to the protein were identified. From the group of appropriate molecules, the researchers were able to identify one that was found to be particularly good. The measure of this is the ability of the molecule to bind effectively to the target protein, but without disrupting the activity of other proteins in a way that may be toxic to the body.
In the long search for the molecules, the researchers used methods that make it possible to monitor, in the laboratory and in living cells, the irreversible microscopic connections between the molecules and proteins and to test their function in different situations. With the discovery of the most efficient molecule, the name Sulfopin – the bread between Sulfolane – the name of a chemical group discovered in some of the molecules linked to Pin1 – and the name of the protein itself.
Next, the researchers conducted experiments that focused on two types of cancer that Pin1 is known to contribute to their development: a brain cancer of a type that is mostly common in children and pancreatic cancer. Initially, experiments were performed on cells in the laboratory, and it was found that the effect of the molecule is relatively small in the first few days, but after about a week, its effect accumulates – and it manages to significantly delay the rate of cell division. Subsequently, experiments were performed using a cancer model in mice and fish, and it was found that thanks to the molecule’s effect on Pin1 and other proteins it activates, the development of tumors in these animals was significantly inhibited, and they survived longer.
To advance the possibility of translating the scientific findings into the clinic, Yeda, the intellectual property arm of the institute’s scientists, has registered a patent for the molecule that is already attracting interest among biotech companies that are considering investing in preclinical research. However, it is important to note that the road to a hospital bed is still long: on average, it takes more than a decade of research and development work and an investment of $ 2-1 billion – with very small chances of success – to reach, perhaps, the desired goal: creating a new cancer drug.
Researchers from the Center for Cancer Research in London, the University of Saarland in Germany, the University of Health and Science in Portland, Peking University in Beijing, Mount Sinai Hospital in New York, the Children’s Hospital in Boston and Stanford University participated in the study. The study was led by Dr. Christian Dubiala, a postdoctoral researcher from Dr. London’s Laboratory, and Dr. Benika Finch, a research student in Prof. Gray’s laboratory.
More on the subject on the Yadan website: