Microcystins – leads for anticancer drugs

In one of my first blog posts I have shortly discussed that the hepatotoxic microcystins, cyclic peptides from cyanobacteria, are currently studied for their potential as leads for anticancer drugs. I also mentioned a poster we presented at the ICNPR 2012 in New York.

Recently, the paper covering our work in this field has been published in PLOS ONE. It describes the cytotoxic potency and the OATP1B1/1B3 transporter selectivity of 23 naturally occurring microcystin congeners. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. We found that microcystin structure has a significant impact on transporter selectivity, and thus it should potentially be possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs (some cancer types express OATP1B3 and could thus be targeted; for more information see the paper…).

For the figure depicting the chemical structure of microcystins / nodularins I have compiled a list of all congeners described in the literature to date. The data are available at figshare. If you are interested in microcystins you should definitely take a look at this list.

Interestingly, some weeks ago I met a synthetic chemist at a conference who works on a microcystin synthesis, and we started talking about a collaboration. This will be a great opportunity to further explore the chemical space around the microcystins, hopefully leading to derivatives with higher selectivity, potency and better pharmacokinetic properties…