The correlation of experimental microsomal stability with redox properties of drugs

The use of molecular descriptors, which are based on physiochemical properties of the corresponding organic molecules, are used to determine the drug-likeness of potential pharmaceuticals. Until now only molecular descriptors, which reflect the solubility profiles of the compounds are used. An important attribute of drugs is their metabolic stability and the current molecular descriptors do not address this indispensable property. The ionisation potentials (IP, one-electron oxidation) and electron affinities (EA, one-electron reduction) can be calculated and potentially used as effective molecular descriptors. However, they need to be linked to experimental data to demonstrate their utility. The standard assay to determine metabolic stability is the microsomal stability assay, which measures intrinsic drug clearance. Results from the literature will be collected and correlated against their calculated IP and EA values to establish whether these properties can be used to better define promising regions in chemical space.


Aim and objectives: the aim is to collate a substantial number of organic compounds with experimentally derived clearance values from the literature. The overall objective is to establish whether the experimental results correlate with calculated redox properties of the compound