Inobrodib [ino-bro-dib
]
A first-in-class oral cancer drug
Inobrodib is a small molecule inhibitor taken orally as a capsule, and is the most advanced investigational treatment of its type. It inhibits p300 and CBP by binding into the conserved bromodomain of the twin proteins. Inobrodib displaces these two transcription co-activation factors to other parts of chromatin, rather than causing their degradation. This impacts the expression of key cancer drivers, including MYC and IRF4. Different cancer indications can be targeted by inobrodib as monotherapy and in combination with existing standard of care drugs.
The science behind inobrodib
Inhibiting p300/CBP impacts the expression of key cancer drivers
Inobrodib selectively displaces p300/CBP and, as a result, impacts the expression of key cancer driving genes. In particular, MYC and IRF4 are significantly affected by p300/CBP inhibition. They are important in the progression of multiple myeloma in particular.
An oral treatment for real-world settings
Inobrodib is a new type of investigational treatment, primarily being developed for people living with multiple myeloma. Delivered as an oral capsule, the drug is designed to be easy for patients to take at home without the need for intensive monitoring. Inobrodib has a favorable safety profile for a drug in this setting, so it may also be an optimal treatment option for people who are unable to tolerate other cancer treatments.
Targeting the bromodomain of p300 and CBP
A differentiated and highly selective inhibitor
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. There are over 60 different bromodomains on cellular proteins, many of which constitute potential drug targets.
Inobrodib selectively displaces p300/CBP from regions of the chromatin that are important for oncogenic activity, called super-enhancer sites. This is a key differentiator from inhibitors that target the HAT catalytic site or degraders (e.g. PROTACs) that eliminate p300/CBP.
In breadth-of-efficacy cell panel testing, inobrodib has a very specific effect on clusters of cancer types, rather than being generally cytotoxic.
Enhancing standard of care agent efficacy
In both pre-clinical and clinical studies, inobrodib has been shown to combine well with several approved therapies. Notably, inobrodib synergizes with the IMiD class of drugs used extensively to treat multiple myeloma. Other promising combinations include with bi-specific antibodies and checkpoint inhibitors, and to enhance the activity of DNA damage repair inhibitors.
Scientific publications, posters and presentations
View and download posters from recent key conferences
Tolerability and clinical activity of novel first-in-class oral agent, inobrodib (CCS1477), in combination with pomalidomide and dexamethasone in relapsed/refractory multiple myeloma
Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies
CellCentric’s Director of Cancer Biology talks inobrodib’s mechanism of action in the context of latest efficacy and safety data, treating late/last stage multiple myeloma
Tolerability and clinical activity of novel first in class oral agent, inobrodib (CCS1477), in combination with pomalidomide and dexamethasone in relapsed/ refractory multiple myeloma