In Silico Tools to Extract the Drug Design Information Content of Degradation Data: The Case of PROTACs Targeting the Androgen Receptor.

ABSTRACT: Proteolysis-Targeting Chimeras (PROTACs) have recently emerged as a promising technology in the drug discovery landscape. Large interest in the degradation of the androgen receptor (AR) as a new anti-prostatic cancer strategy has resulted in several papers focusing on PROTACs against AR. This study explores the potential of a few in silico tools to extract drug design information from AR degradation data in the format often reported in the literature. After setting up a dataset of 92 PROTACs with consistent AR degradation values, we employed the Bemis-Murcko method for their classification. The resulting clusters were not informative in terms of structure-degradation relationship. Subsequently, we performed Degradation Cliff analysis and identified some key aspects conferring a positive co

SUBMITTER: Apprato G 

PROVIDER: S-EPMC9919651 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature