Chapter 5 Recent Advances on in silico ADME Modeling

Although significant progress has been made on high-throughput screening (HTS) of absorption, distribution, metabolism and excretion (ADME), toxicity, and pharmacokinetic properties in drug discovery, the in silico ADME and toxicity (ADME-Tox) prediction still plays an important role in facilitating pharmaceutical companies to select drug candidates wisely prior to expensive clinical trials. Unlike in vitro or in vivo ADME-Tox assays, in silico ADME-Tox is particularly efficient and cheap to search a great number of compounds in screening libraries or virtual molecules in combinatorial chemistry prior to synthesizing them. In the last several years, a lot of new ADME-Tox models have been published and many new software packages and ADME-Tox databases have emerged. In this review, we will present the advances on some oral administration related ADME properties, which include aqueous solubility, Caco-2 and MDCK permeability, blood-brain barrier (BBB), human intestinal absorption (HIA), plasma protein binding (PPB), as well as oral bioavailability (F). We will not only simply review the recent published models but also provide our deep insight on how to construct more accurate and reliable ADME-Tox models.