Cancer drug discovery
An exploratory programme investigating polyketides with novel mechanisms of action with potential relevance to cancer.
Polyketides are a rich source of cancer therapeutics
Doxorubicin and epirubicin are among the oldest polyketide-based cancer therapeutics. More recently, temsirolimus, a derivative of rapamycin, has been approved in renal cancer, and ixapebilone, an epothilone, has been approved in breast cancer. Furthermore, there is a rich pipeline of clinical development projects based on polyketides.
Polyketides uniquely address difficult cancer targets
Crucially, polyketides are often the first or the only compounds to address specific targets; mTOR, the target of temsirolimus, is an example of this. Polyketides may be particularly effective at disrupting protein-protein interactions. As another example, the spliceosome is a promising target in cancer due to the large number of cancer-associated proteins that have alternate splice-forms. Three compounds are known to be spliceosome modulators, all of them polyketides.
Biotica’s exploratory programmes
Biotica regularly reviews polyketide leads with novel mechanisms of action against cancer. These do not meet Biotica’s usual criterion for development of having a clinically validated target, but the unmet need in cancer is such that both potential licensing partners and the oncologists who will ultimately be prescribing the drugs are receptive to novel mechanisms of action. Biotica has a number of such programmes in the exploratory stages, looking at targets including the spliceosome and grp78.
