Developing degraders: principles and perspectives on design and chemical space. Issue 10 (12th August 2019)

• Record Type: Journal Article
• Authors: Maple, Hannah J.; Clayden, Nat; Baron, Anne; Stacey, Callum; Felix, Robert
• Is Part Of: MedChemComm. Volume 10:Issue 10(2019)
• Page Start: 1755
• Page End: 1764
• Publication Date: 2019-08-12
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c9md00272c
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Degraders ( e.g. PROTACs, SNIPERs, degronimers etc. ) are a new modality offering increasing potential both as tools for basic research and therapeutic development. Abstract : Degraders ( e.g. PROTACs, SNIPERs, degronimers etc. ) are a new modality offering increasing potential both as tools for basic research and therapeutic development. They occupy chemical space that lies outside the classical Lipinski 'Rule of 5', which poses fresh challenges for achieving cell permeability and oral bioavailability. This study presents a comprehensive database of degrader structures from the peer reviewed literature, including both optimized degraders and first generation compounds, in order to provide a thorough assessment of the chemical space associated with this modality and identify common trends used during the 'hit to lead' process. The results provide insights into this new area of chemical space as well as pointers for degrader design, which we anticipate will be useful for researchers entering this field.