Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

STX140, a bis-sulfamate derivative of the endogenous steroid 2-methoxyestradiol, has shown promising anti-cancer potency both in vitro and in vivo, with excellent bioavailability. Its activity against taxane-resistant xenografts make it a potential drug candidate against triple negative breast cancer (TNBC). These properties are linked to the ability of STX140 to act in a multi-targeting fashion in vivo as a microtubule disruptor, leading to cell cycle arrest and with both pro-apoptotic and anti-angiogenic activities. Carbonic Anhydrase IX (CA IX) is a well-established biomarker for aggressive cancers, including TNBC. This study reports, for the first-time, the inhibitory activities of a series of steroidal and non-steroidal sulfamate derivatives against CA IX in comparison to the ubiquitous CA II, with some compounds demonstrating 100-200 fold selectivity for CA IX over CA II. X-ray crystallographic studies of four of the most promising compounds reveal isoform specific residue interactions responsible for the high specificity.

Original publication

DOI

10.1021/acs.jmedchem.8b01990

Type

Journal article

Journal

J Med Chem

Publication Date

05/02/2019