AZ9567

Potency assay (off target): The selectivity of AZ'9567 was investigated to assess its suitability as a quality in vivo tool with which to investigate MAT2A biology. Secondary pharmacology profiling of AZ'9567 demonstrated good off target selectivity when tested against a total of 86 targets. These targets represent a broad pharmacological space consisting of enzymes, membrane transporters, G-protein-coupled receptors (GPCRs), kinases, nuclear hormone receptors, and ion channels (data generated at Eurofins). AZ'9567 showed measurable activity (Ki and IC50) against 12 off-targets below 10 μM, with one of these off-targets, the adenosine transporter, being below 1 μM potency and showing antagonist behavior in a follow-up functional assay. In addition, AZ'9567 showed no PXR induction at 1 μM and only a 4-fold increase at 10 μM.

Potency assay, off target (cells): AZ'9567 was also characterized in a broad suite of in vitro cell-based assays representing hepatic, cardiac, mitochondrial, and general cytotoxicity, which revealed a lack of effect in all assays.