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 and IRF4. Different cancer indications can be targeted by inobrodib as monotherapy or in combination with existing standard of care drugs. It is the most advanced drug of its type.

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 displaces p300/CBP, and as a result, impacts the expression of key cancer driving genes. MYC and IRF4 are significantly affected by p300/CBP inhibition. They are important in progression of haematological malignancies. p300/CBP inhibition also impacts the androgen receptor expression, which is critical in late stage prostate cancer, and the immune checkpoint protein PDL1.

An oral treatment for real world settings

Inobrodib is a new type of treatment for people with cancer. Delivered as an oral capsule, it is easy for patients to take. Inobrodib can be used at home without the need for intensive monitoring. As it has a good safety profile for a drug in this setting, it can also be used by those who are unable to tolerate other treatments, including the elderly and frail.

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, as has targeting another protein pocket, the CH1 domain. CellCentric instead chose to focus on targeting the conserved bromodomain pockets of p300/CBP. This can also profoundly impact p300/CBP function and genomic localization. To date it seems that binding into the bromodomain gives the best balance of potency, selectivity and desired effects, delivering a clear therapeutic window.

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. 

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