Design and Synthesis of Novel Cereblon Binders for Use in Targeted Protein Degradation
Stephen Norris
1
,
Xiaochu Ba
1
,
Jayce Rhodes
1
,
Dehua Huang
1
,
Gody Khambatta
1
,
Jennifer Buenviaje
1
,
Surendra Nayak
1
,
Surendra K. Nayak
1
,
Joseph Meiring
1
,
Samantha Reiss
1
,
Samantha M. Reiss
1
,
Shuichan Xu
1
,
Lihong Shi
1
,
Brandon Whitefield
1
,
Matt Alexander
1
,
Evan J Horn
1
,
Matthew Correa
1
,
Lida Tehrani
1
,
Joshua D Hansen
1
,
Patrick Papa
1
,
Deborah S Mortensen
1
Publication type: Journal Article
Publication date: 2023-11-22
scimago Q1
wos Q1
SJR: 1.801
CiteScore: 11.5
Impact factor: 6.8
ISSN: 00222623, 15204804
PubMed ID:
37991844
Drug Discovery
Molecular Medicine
Abstract
Modulating the chemical composition of cereblon (CRBN) binders is a critical step in the optimization process of protein degraders that seek to hijack the function of this E3 ligase. Small structural changes can have profound impacts on the overall profile of these compounds, including depth of on-target degradation, neosubstrate degradation selectivity, as well as other drug-like properties. Herein, we report the design and synthesis of a series of novel CRBN binding moieties. These CRBN binders were evaluated for CRBN binding and degradation of common neosubstrates Aiolos and GSPT1. A selection of these binders was employed for an exploratory matrix of heterobifunctional molecules, targeting CRBN-mediated degradation of the androgen receptor.
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Metrics
37
Total citations:
37
Citations from 2025:
22
(59.46%)
Cite this
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RIS |
BibTex |
MLA
Cite this
GOST
Copy
Norris S. et al. Design and Synthesis of Novel Cereblon Binders for Use in Targeted Protein Degradation // Journal of Medicinal Chemistry. 2023. Vol. 66. No. 23. pp. 16388-16409.
GOST all authors (up to 50)
Copy
Norris S., Ba X., Rhodes J., Huang D., Khambatta G., Buenviaje J., Nayak S., Nayak S. K., Meiring J., Reiss S., Reiss S. M., Xu S., Shi L., Whitefield B., Alexander M., Horn E. J., Correa M., Tehrani L., Hansen J. D., Papa P., Mortensen D. S. Design and Synthesis of Novel Cereblon Binders for Use in Targeted Protein Degradation // Journal of Medicinal Chemistry. 2023. Vol. 66. No. 23. pp. 16388-16409.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1021/acs.jmedchem.3c01848
UR - https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01848
TI - Design and Synthesis of Novel Cereblon Binders for Use in Targeted Protein Degradation
T2 - Journal of Medicinal Chemistry
AU - Norris, Stephen
AU - Ba, Xiaochu
AU - Rhodes, Jayce
AU - Huang, Dehua
AU - Khambatta, Gody
AU - Buenviaje, Jennifer
AU - Nayak, Surendra
AU - Nayak, Surendra K.
AU - Meiring, Joseph
AU - Reiss, Samantha
AU - Reiss, Samantha M.
AU - Xu, Shuichan
AU - Shi, Lihong
AU - Whitefield, Brandon
AU - Alexander, Matt
AU - Horn, Evan J
AU - Correa, Matthew
AU - Tehrani, Lida
AU - Hansen, Joshua D
AU - Papa, Patrick
AU - Mortensen, Deborah S
PY - 2023
DA - 2023/11/22
PB - American Chemical Society (ACS)
SP - 16388-16409
IS - 23
VL - 66
PMID - 37991844
SN - 0022-2623
SN - 1520-4804
ER -
Cite this
BibTex (up to 50 authors)
Copy
@article{2023_Norris,
author = {Stephen Norris and Xiaochu Ba and Jayce Rhodes and Dehua Huang and Gody Khambatta and Jennifer Buenviaje and Surendra Nayak and Surendra K. Nayak and Joseph Meiring and Samantha Reiss and Samantha M. Reiss and Shuichan Xu and Lihong Shi and Brandon Whitefield and Matt Alexander and Evan J Horn and Matthew Correa and Lida Tehrani and Joshua D Hansen and Patrick Papa and Deborah S Mortensen},
title = {Design and Synthesis of Novel Cereblon Binders for Use in Targeted Protein Degradation},
journal = {Journal of Medicinal Chemistry},
year = {2023},
volume = {66},
publisher = {American Chemical Society (ACS)},
month = {nov},
url = {https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01848},
number = {23},
pages = {16388--16409},
doi = {10.1021/acs.jmedchem.3c01848}
}
Cite this
MLA
Copy
Norris, Stephen, et al. “Design and Synthesis of Novel Cereblon Binders for Use in Targeted Protein Degradation.” Journal of Medicinal Chemistry, vol. 66, no. 23, Nov. 2023, pp. 16388-16409. https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01848.