Anticancer —BAY-59-8862
The Pacific yew tree extract paclitaxel (Taxol) was hailed as a wonder drug for the treatment of cancer in the 1990s. It is extremely expensive, as it is present in only tiny amounts in the bark of Taxus brevifolia, but semisynthetic methods have been developed for its synthesis from compounds found in related trees. Another taxane analogue, docetaxel (Taxotere), is isolated from the needles of the tree Taxus baccata, and taxanes are now in regular use in the treatment of a range of cancers, especially lung, breast and ovarian tumours.
The compounds inhibit microtubule depolymerisation, and promote the assembly of microtubules, disrupting mitotic function and cell arrest. However, tumours are often naturally insensitive, and clinical resistance can develop. Studies are now under way to find analogues that avoid this multi drug resistance.
The 14β-hydroxy-10-deacetylbaccatin III analogue, originally coded IDN 5109 and now referred to as BAY 59-8862, looks particularly promising.1 Originally discovered by the Italian company Indena and licensed to Bayer, it is effective against a wide range of different tumours, notably those that display resistance to paclitaxel.
Studies in a variety of human tumour xenografts in mice showed it was active against several tumours with either natural or acquired resistance to paclitaxel.2 It was also effective against numerous tumours resistant to either or both cisplatin or doxorubicin, and in all these cases, it was found to be at least as effective as paclitaxel.
It is more water-soluble than paclitaxel, and is better at crossing the blood–brain barrier, which means it may be of use against brain tumours. The compound is one of a number of taxane derivatives currently in clinical trials, including several that are being looked at by Bristol-Myers Squibb.
The prospects for one or more second-generation taxanes with improved activity reaching the market are good.