Your browser doesn't support javascript.
loading
Characterisation of high throughput screening outputs for small molecule degrader discovery.
Bell, Lillie E; Bardelle, Catherine; Packer, Martin J; Kastl, Johanna; Holdgate, Geoffrey A; Davies, Gareth.
Afiliação
  • Bell LE; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-BioCenter 1, 1030 Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, 1030, Vienna, Austria.
  • Bardelle C; Hit Discovery, Discovery Sciences, R&D, AstraZeneca, Alderley Park, Macclesfield, UK.
  • Packer MJ; TDE, Oncology, R&D, AstraZeneca, Cambridge, UK.
  • Kastl J; Assay.Works GmbH, Am Biopark 11, Regensburg, Germany.
  • Holdgate GA; Hit Discovery, Discovery Sciences, R&D, AstraZeneca, Alderley Park, Macclesfield, UK. Electronic address: geoff.holdgate@astrazeneca.com.
  • Davies G; Hit Discovery, Discovery Sciences, R&D, AstraZeneca, Alderley Park, Macclesfield, UK.
SLAS Discov ; 29(5): 100162, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38797285
ABSTRACT
Targeted protein degradation is an important mechanism carried out by the cellular machinery, one that is gaining momentum as an exploitable strategy for the development of drug-like compounds. Molecules which are able to induce proximity between elusive therapeutic targets of interest and E3 ligases which subsequently leads to proteasomal degradation of the target are beginning to decrease the percentage of the human proteome described as undruggable. Therefore, having the ability to screen for, and understand the mechanism of, such molecules is becoming an increasingly attractive scientific focus. We have established a number of cascade experiments including cell-based assays and orthogonal triage steps to provide annotation to the selectivity and mechanism of action for compounds identified as putative degraders from a primary high throughput screen against a high value oncology target. We will describe our current position, using PROTACs as proof-of-concept, on the analysis of these novel outputs and highlight challenges encountered.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bibliotecas de Moléculas Pequenas / Descoberta de Drogas / Ensaios de Triagem em Larga Escala / Proteólise Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bibliotecas de Moléculas Pequenas / Descoberta de Drogas / Ensaios de Triagem em Larga Escala / Proteólise Idioma: En Ano de publicação: 2024 Tipo de documento: Article