Global competition targets 'undruggable' cancer protein

A new global competition offering over US$500,000 in prizes aims to spur drug discovery breakthroughs for the cancer target known as TBXT.

TBXT (also called Brachyury) is implicated in multiple tumour types, including breast, lung, colon and prostate cancers. It is also a defining feature and key vulnerability of chordoma, a rare and difficult-to-treat bone cancer. Unlike many other cancer-related proteins, TBXT is absent in most normal cells, making it an attractive and specific target for cancer therapies.

TBXT belongs to a class of proteins called transcription factors which, though implicated in many diseases, have historically been considered ‘undruggable’. However, new therapeutic modalities and technological advances, such as in chemical biology and artificial intelligence (AI), offer the potential to overcome these historical obstacles.

To realise that potential, the Chordoma Foundation, with support from multiple philanthropic partners, has launched the TBXT Challenge, which offers prizes for reaching key milestones in TBXT drug discovery. The inaugural prize, with a purse of US$500,000, will reward the discovery of compounds that bind potently to the TBXT protein — a crucial step in developing inhibitors or targeted protein degraders.

Two prize levels are available: US$250,000 for compounds with dissociation constant (K_d) less than 300 nM and US$100,000 for K_d less than 1 μM. Up to three teams can win the prize.

Companies and academic investigators can submit up to 96 compounds for free biophysical evaluation by the Chordoma Foundation’s laboratory, CF Labs. The foundation also offers scientific resources to assist prize competitors, and a suite of preclinical and clinical research capabilities to enable subsequent development of winning compounds. All competitors will retain ownership of their intellectual property and data.

“With the TBXT Challenge, we invite drug discovery innovators to partner with us to validate new approaches capable of achieving breakthroughs in drugging difficult targets like TBXT,” said Josh Sommer, Executive Director of the Chordoma Foundation. “We hope this will not only accelerate discovery of urgently needed TBXT drugs, but may also set a precedent for other targets currently considered undruggable.”

For more information on the competition, visit https://tbxtchallenge.org/.

Image credit: iStock.com/Kristina Ratobilska