Development of anti-cancer Candidate Drug with unique mechanism

Purpose and goal

The aim was to develop HDAC6 inhibitors with sufficiently good drug properties to enable in-vivo efficacy studies. This has succeeded both for a series of substances active against HDAC6 only, and for a series with a unique mechanism of action active against both HDAC6 and an additional cancer target protein. The goal is to show effect in a relevant animal cancer model. Two substances (one from each series) are now evaluated in an in-vivo efficacy study in a multiple myeloma mouse model where positive results would provide a solid basis for the further development towards clinical trials.

Expected results and effects

In an ambitious chemistry program, more than 450 substances have been synthesized and their effects tested against HDAC isoforms and against cancer cells as well as healthy cells. Two series of isoform-selective HDAC6 inhibitors with good drug properties have been developed, one of which has a unique mechanism of action by inhibiting an additional cancer target protein. Functional studies have shown that the latter substances are likely to have a therapeutic advantage over pure HDAC6 inhibitors. Two patent applications have been submitted covering all substances of interest today.

Planned approach and implementation

The two project partners, the research company Kancera and Cancer Center Karolinska (CCK), have covered a large part of the capacity and skills required to drive the project to the current phase. Kancera has been responsible for chemistry and in vitro analyzes while CCK has performed functional biology studies. In-vivo studies, X-ray crystallography and ADME analyzes have been performed by various contract research companies.