Domain-specific BET bromodomain inhibitors for cancer

Domain-specific BET bromodomain inhibitors for cancer

Partnering opportunity in cancer: 

Domain-specific BET bromodomain inhibitors for cancer



Associate Professor Chris Burns, Professor Andrew Wilks


The BET family of bromodomain-containing proteins consists of BRDT, BRD2, BRD3 and BRD4. Whilst BRDT expression is restricted to the testes, BRD2, 3 and 4 are expressed ubiquitously. These proteins bind to acetylated lysine residues on histones H3 and H4 where they play an important role in transcriptional control. Deletion or inhibition of BRD4 is highly effective in inhibiting c-myc-dependent tumour growth.

Key inflammatory genes are also down regulated by inhibition of BET bromodomains, conferring protection against endotoxic shock and bacteria-induced sepsis.

As a consequence of the promising data reported in preclinical studies using pan-BET inhibitors, at least ten pan-BET inhibitors have entered clinical trials.

The technology

We have undertaken a program to identify novel and potent inhibitors of BET bromodomains that have differential activity across the family.

Late lead optimisation is underway to further improve selectivity, potency and pharmacokinetics. X-ray crystallography demonstrates a novel binding mode of the lead compound, and ADMET studies indicate selected compounds possess promising pharmacokinetic and drug-like properties.


BET Bromodomain family members are implicated in many cancers including leukemia, lymphoma, multiple myeloma and c-myc-driven cancers.

Compounds identified in this program may also have potential anti-inflammatory effects. These compounds will be instrumental to further characterising the role of each member of the BET Bromodomain family in biology and disease.

Intellectual property

A PCT application has been filed for compound structures from one chemical series, whilst a second series has not been publicly disclosed. An opportunity exists to enhance and protect novel intellectual property.

Opportunity for partnership

This project is licensed to Catalyst Therapeutics, a spinout from the Walter and Eliza Hall Institute.

Catalyst Therapeutics is seeking a partner to co-invest in the final stages of lead optimisation and preclinical testing of these novel small molecule compounds.

The ultimate goal is to develop an orally available small molecule candidate and back up compounds with appropriate potency, safety and pharmacokinetic profiles. We have a successful track record in medicinal chemistry programs focused on hit-to-lead and lead optimisation.

Key publication

  • Sharp PP. et al. 2014. Evaluation of functional groups as acetyl-lysine mimetics for BET bromodomain inhibition. Medicinal Chemical Communications. 5(12) 1834-42


Dr David Segal, Technology Development Associate

Phone: +61 3 9345 2418 Email:


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