Abstract
Promoting a preclinical small molecule candidate to clinical phases is a high-risk decision taken on the basis of a large amount of heterogenous in vitro and in vivo data that may, or may not, translate into humans. Collecting safety data along the path from preclinical, through clinical and all the way up to the post-marketing life of a drug provides a unique perspective of the correspondence, validity, evolution, and detection of drug safety signals.
Chemotargets CLARITY is an integrative drug discovery platform widely used across pharmaceutical companies, large academic institutions and non-for-profit organizations worldwide [1,2]. It uses artificial intelligence on carefully curated data to connect molecules, protein targets, safety events, and therapeutic indications with the help of state-of-the-art analytics tools. Beyond a knowledge-based source that can be interrogated from any discovery angle, the platform can be used to identify the probable primary and secondary targets of small molecules and their predicted metabolites by rapidly profiling through consensus ligand-based models of 4,799 proteins built from affinity data for almost 3 million small molecules. In addition, machine learning models of 1,278 safety endpoints were constructed from data extracted from almost 16 million spontaneous reports, including hundreds of safety-related mechanisms annotated with preclinical toxicity and clinical safety issues.
The new version of Chemotargets CLARITY (version 5) will offer a new translational drug safety dashboard that will allow users to analyze the evolution of safety issues for a given drug, from the initial preclinical stages in animals to the post-marketing exposure to humans.
[1] Ellis et al. (2020) Evaluating kratom alkaloids using PHASE. PLoS ONE 15, e0229646.
[2] Ellis et al. (2019) Assessing the structural and pharmacological similarity of newly identified drugs of abuse to controlled substances using Publich Health Assessment via Structural Elucidation. Clin. Pharmacol. Ther. 106, 116-122.
