Open AccessSystematic Investigation of the Permeability of Androgen Receptor PROTACs
Author(s) -
D.E. Scott,
Timothy P. C. Rooney,
Elliott D. Bayle,
Tashfina Mirza,
Henriëtte M. G. Willems,
Jonathan H. Clarke,
Stephen P. Andrews,
John Skidmore
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00194
Subject(s) - ubiquitin ligase , androgen receptor , bifunctional , drug discovery , dna ligase , chemistry , ubiquitin , receptor , microbiology and biotechnology , computational biology , biochemistry , biology , medicine , enzyme , prostate cancer , cancer , gene , catalysis
Bifunctional molecules known as PROTACs simultaneously bind an E3 ligase and a protein of interest to direct ubiquitination and clearance of that protein, and they have emerged in the past decade as an exciting new paradigm in drug discovery. In order to investigate the permeability and properties of these large molecules, we synthesized two panels of PROTAC molecules, constructed from a range of protein-target ligands, linkers, and E3 ligase ligands. The androgen receptor, which is a well-studied protein in the PROTAC field was used as a model system. The physicochemical properties and permeability of PROTACs are discussed.