The article deals with the development of bile acid modulators as drugs and how to identify substances with a risk of causing cholestasis in the early stages of discovery. He emphasizes that bile acids have a complex biology and can be toxic to the liver when modulated incorrectly. It describes the importance of thoughtful DMPK (drug fate study - absorption, distribution, metabolism, excretion) strategies to reveal the cholestatic potential of candidate molecules. He states that close collaboration of teams from different fields (biology, pharmacokinetics, toxicology, clinical) is key in safety assessment. The article also highlights the important role of CDMO companies that provide technological and professional support during the development of these drugs. The goal of the described approach is to select candidates with a reduced risk of cholestasis and increase the chance that they will safely enter clinical trials and the market.