MassIVE MSV000096172

Partial Public PXD057094

Evaluation of linkers and cereblon-directing warheads for the development of orally bioavailable PROTACs

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Description

PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration. We have previously reported phenyl glutarimide (PG)-based BET PROTAC SJ995973, with improved overall in vitro degradation and antiproliferative activities compared to its direct thalidomide-based analogue dBET1, but similarly poor in vivo pharmacokinetic profile. Here we describe optimization efforts that led to the discovery of an orally bioavailable PG-PROTAC SJ44236, and results of a comprehensive in vitro/vivo comparative study with direct analogues containing alternative CRBN warheads. [doi:10.25345/C5Z31P129] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Targeted protein degradation, PROTACs ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Zoran Rankovic, The Institute of Cancer Research, United Kingdom
Submitting User: msteger
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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
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