Anti-cancer compound wins scientist Biota Award

Walter and Eliza Hall Institute scientist Dr Guillaume Lessene has won this year’s Biota Award for Medicinal Chemistry, awarded by the Royal Australian Chemical Institute.

Dr Lessene, who runs a laboratory in the institute’s Structural Biology Division, won the award for his role in the discovery of several compounds that interact with a protein that has been implicated in the poor response of many cancers to anti-cancer treatments.

The protein is a member of the Bcl-2 family of proteins. This protein family has a role in tumour development, anti-cancer-drug resistance and cancer spread. Dr Lessene’s drug target, in particular, is thought to be involved in the drug resistance of many tumours.

The Biota Award is presented annually to the chemist judged to be responsible for the best drug design and development paper published, patent taken out, or commercial-in-confidence report concerning small molecules as potential therapeutic agents.

Together with eight co-inventors Dr Lessene has made a patent application that describes how his compounds could be used to restore the cell death process that is important in combating the growth of cancers.

Since 2001 Dr Lessene has focused his research on developing small molecules that inhibit the Bcl-2 family of proteins.

“It is expected that drugs targeting Bcl-2-like proteins will have a major impact in cancer treatment,” he said.

Usually, when a cell’s DNA is damaged the cell tries to repair itself and, if it can’t, undergoes a process of programmed cell death.

Cancer develops when, despite cells having DNA damage, they don’t die but continue to divide, leading to tumour formation. This happens when the signal that tells the cell to die is inhibited by Bcl-2 proteins, which allows the cell to keep dividing.

Through high throughput screening, medicinal chemistry, and structure-guided drug design, Dr Lessene and the institute’s drug discovery team have been identifying and refining compounds that inhibit the Bcl-2 proteins.

“From a drug discovery point of view the Bcl-2 proteins are challenging targets because of the size and shape of their binding sites,” Dr Lessene said. “Our successful work therefore represents a considerable achievement, particularly in the field of protein-protein interactions.”

The research leading to the discovery of these compounds is the basis of a collaboration and licensing agreement between the Walter and Eliza Hall Institute, Genentech Inc and Abbott, the leader in Bcl-2 inhibitor development.

Dr Lessene is the second person from the Walter and Eliza Hall Institute to win the Biota Award. Dr Jonathan Baell, also from the Structural Biology Division, received the award in 2004.