Inobrodib [ino-bro-dib

]

A first in class oral anti-cancer drug

Inobrodib is a small molecule inhibitor, taken orally as a capsule. It inhibits p300 and CBP through binding into the conserved bromodomain of the twin proteins. This impacts the expression of key cancer drivers including MYC, IRF4 and the androgen receptor (AR) and its variants. Different cancer indications can be targeted by inobrodib as monotherapy or in combination with existing standard of care drugs. 

The science behind inobrodib

Inobrodib is a small molecule inhibitor drug, developed by CellCentric from initial chemical hits, through to an optimised compound and onto a clinical candidate. 

Inhibiting p300/CBP impacts the expression of key cancers

Inobrodib inhibits p300/CBP, and as a result, impacts the expression of key cancer driving genes. MYC and IRF4 are significantly affected by p300/CBP inhibition, and are important in progression of haematological malignancies. p300/CBP inhibition also impacts the androgen receptor expression, which is critical in late stage prostate cancer. The drug has now completed Phase I evaluation as monotherapy. 

Targeting the bromodomain of p300 and CBP

Developing inhibitors to histone acetyltransferases (HAT) has been of interest for a number of years. Targeting the HAT catalytic active site of p300/CBP has proven challenging. CellCentric instead chose to focus on targeting the conserved bromodomain pockets of p300/CBP. This can also profoundly impact p300/CBP function, and differently from inhibiting the HAT catalytic domain. Other pockets on the proteins can also be targeted (such as CH1). To date it seems that binding into the bromodomain gives the best balance of potency, selectivity and desired effects. 

A differentiated and highly selective inhibitor

There are over 60 different bromodomains on cellular proteins, many of which constitute potential drug targets.

Inobrodib is highly selective for the specific conserved bromodomain of p300 and CBP and shows excellent selectivity against other bromodomains such as BRD1, BRD2, BRD3 and BRD4. Cancer cells that have become resistant to BET inhibitors (for instance JQ1, OTX-015, iBET-151) remain highly sensitive to inobrodib. 

Further underscoring its exquisite selectivity, inobrodib affects the expression of far fewer genes than BET inhibitors whilst maintaining a profound anti-tumour effect.

Inobrodib’s action can be synergistic with BET inhibitors, whilst impacting the expression of 7x fewer genes (compared to JQ1). In breadth-of-efficacy cell panel testing, inobrodib has a very specific effect on clusters of cancer types, rather than being generally cytotoxic.

Scientific publications, posters and presentations

View and download posters from recent key conferences

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