Processing of Biopharmaceutical Profiling Data in Drug Discovery
Kiyohiko Sugano, Kouki Obata, Ryoichi Saitoh, Atsuko Higashida, Hirokazu Hamada · 2007
Since the 1990s and even earlier, Absorption, Distribution, Metabolism, and Excretion (ADME) have been recognized as crucial properties for a successful drug development, because about 40% of development withdrawal has been reported to be derived from poor ADME properties. Therefore, ADME assays and physicochemical assays, which are relevant for ADME, have been incorporated into the lead optimization process. Various medium-to-high-throughput assays have been developed, e.g., octanol/buffer partition coefficients, pKa, solubility, permeability, metabolic stability, drug–drug interactions, protein binding, in vivo pharmacokinetics (PK) studies (cassette dosing), etc. Furthermore, in silico physicochemical and ADME screens including drug likeness calculations have also been incorporated into compound bank library design, combinatorial synthesis design, hit selection, hit-to-lead and lead optimization processes. Today's biopharmaceutical profiling tools in drug discovery are shown.