The human endogenous metabolome as a pharmacology baseline for drug discovery.

The human endogenous metabolome as a pharmacology baseline for drug discovery. Drug Discov Today. 2019 Jun 18;: Authors: Bofill A, Jalencas X, Oprea TI, Mestres J Abstract We have limited understanding of the variation in in vitro affinities of drugs for their targets. An analysis of a highly curated set of 442 interactions between 293 drugs and 79 primary targets reveals that 67% of drug-target affinities have values above that of the corresponding endogenous ligand, 96% of them fitting within a range of two orders of magnitude. Our findings suggest that the evolutionary optimised affinity of endogenous ligands for their native proteins can serve as a baseline for the primary pharmacology of drugs. We show that the degree of off-target selectivity and safety risks of drugs derived from their secondary pharmacology depend very much on that baseline. Thus, we propose a new approach for estimating safety margins. PMID: 31226432 [PubMed - as supplied by publisher]
Source: Drug Discovery Today - Category: Drugs & Pharmacology Authors: Tags: Drug Discov Today Source Type: research