Despite enormous investments in pharmaceutical research and development, the number of approved drugs has declined in recent years. The attrition of compounds under development is dramatically high. Safety, insufficient efficacy and, to some extent, absorption, distribution, metabolism, excretion and toxicity (ADMET) problems are the responsible factors. Formerly, drugs were discovered by testing compounds synthesized in time - consuming multistep processes against a battery of in vivo biological screens. Promising compounds were then further tested in development, where their pharmacokinetic (PK) properties, metabolism and potential toxicity were investigated. Adverse fi ndings were often made at this stage and projects were re - started to find another clinical candidate. Drug discovery has undergone a dramatic change over the last two decades due to a methodological revolution including combinatorial chemistry, high - throughput screening and in silico methods, which greatly increased the speed of the process of drug finding and development.