| Title: |
Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766). |
| Authors: |
Chessum, NEA; Sharp, SY; Caldwell, JJ; Pasqua, AE; Wilding, B; Colombano, G; Collins, I; Ozer, B; Richards, M; Rowlands, M; Stubbs, M; Burke, R; McAndrew, PC; Clarke, PA; Workman, P; Cheeseman, MD; Jones, K |
| Contributors: |
Chessum, Nicola; Caldwell, John; Collins, Ian; Ozer, Bugra; Burke, Rosemary; Clarke, Paul; Workman, Paul; Cheeseman, Matthew; Jones, Keith |
| Publisher Information: |
AMER CHEMICAL SOC |
| Publication Year: |
2017 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
Cell Line; Cell Survival; Protein Conformation; Models; Molecular; Proteolysis; Prion Proteins |
| Description: |
Demonstrating intracellular protein target engagement is an essential step in the development and progression of new chemical probes and potential small molecule therapeutics. However, this can be particularly challenging for poorly studied and noncatalytic proteins, as robust proximal biomarkers are rarely known. To confirm that our recently discovered chemical probe 1 (CCT251236) binds the putative transcription factor regulator pirin in living cells, we developed a heterobifunctional protein degradation probe. Focusing on linker design and physicochemical properties, we generated a highly active probe 16 (CCT367766) in only three iterations, validating our efficient strategy for degradation probe design against nonvalidated protein targets. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; 933; application/pdf |
| Language: |
English |
| ISSN: |
1520-4804; 0022-2623 |
| Relation: |
Journal of medicinal chemistry, 2018, 61 (3), pp. 918 - 933; https://repository.icr.ac.uk/handle/internal/971 |
| DOI: |
10.1021/acs.jmedchem.7b01406 |
| Availability: |
https://doi.org/10.1021/acs.jmedchem.7b01406; https://repository.icr.ac.uk/handle/internal/971 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.92EC246F |
| Database: |
BASE |