In pharmaceutical research, solubility plays a key part in the assessment of pharmacokinetic risks. Poor drug absorption, reduced efficacy, excessive metabolism, and adverse reactions are frequently related to issues of drug solubility. During early discovery research at pharmaceutical companies, many thousands of molecules are considered. Most are rejected due to perceived unfavorable properties. Here the author uses the Wiki-pS0TM database, which forms the backbone of this unique handbook. Also discussed is the emerging class of therapeutically promising research molecules called PROTACs (proteolysis-targeting chimeras), showing a propensity for ˜undruggable targets.FEATURES¢ A comprehensive and unique listing of measured aqueous intrinsic solubility focusing on drug-like and drug-relevant molecules.¢ The database can be used to predict the solubility of research pharmaceutical molecules.¢ Includes downloadable files of the database (.csv format).¢ The mining of the database can result in a better design of solubility assay protocols, leading to better quality of measurements.¢ Artificial intelligence and Bayesian statistics will likely be key to this subject area in the future.Alex Avdeef has been an American Association of Pharmaceutical Scientists (AAPS) Fellow since 2014, a former visiting senior research fellow at Kings College London, and is the author of Absorption and Drug Development (2nd ed., Wiley, 2012). In 2021, the book was translated into Chinese, by translators affiliated with the China Food and Drug Administration. For nearly 50 years, he has been teaching, researching, and developing methods, instruments, and analysis software for the measurement of ionization constants, solubility, dissolution, and permeability of drugs. His accomplishments in the development of instrumentation include several well-known instruments that are or recently have been manufactured by leading companies in the instrument market, including Thermo Fisher Scientific, Sirius Analytical, and Pion Inc. He has over 200 technical publications in primary scientific journals and book chapters. He has written several comprehensive technical guides and is a co-inventor on six patents. He cofounded Sirius Analytical (UK) in 1989, pION Inc. (USA) in 1996, and founded in“ADME Research (New York City) in 2011. His other positions were at Orion Research, Syracuse University, UC Berkeley, and Caltech.