2. Academic Validation
  3. Synthesis and Structure-Activity Relationships of CRBN-Recruiting ZBTB11 Molecular Glue Degraders

Synthesis and Structure-Activity Relationships of CRBN-Recruiting ZBTB11 Molecular Glue Degraders

  • J Med Chem. 2025 Sep 25;68(18):19287-19302. doi: 10.1021/acs.jmedchem.5c01352.
Jiewei Jiang 1,  Nathan L Tran 1 2,  Emma Svendsen 2,  Eric S Wang 2,  Fleur M Ferguson 1 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, United States.
  • 2 Center for Therapeutics Discovery, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, United States.
  • 3 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States.
PMID: 40911408 DOI: 10.1021/acs.jmedchem.5c01352
Abstract

Rational optimization of molecular glue degraders (MGD) remains a challenging and lengthy process even after identification of a promising scaffold. Unlike proteolysis targeting chimeras (PROTAC), MGDs rely on induced protein-protein interactions as opposed to direct binding in order to target a protein of interest for degradation. Here, we report the synthesis of MGDs targeting the transcription factor ZBTB11 guided by protein complex modeling. Exploration of structure-activity-relationships yielded JWJ-01-306 with improved ZBTB11 degradation activity and potent antiproliferative effects against BRAF inhibitor-resistant melanoma cells. Our findings led to the discovery of a novel MGD that targets a previously undrugged transcription factor with the potential to address acquired resistance to Cancer therapy.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-14660
    99.94%, BRAF抑制剂
    Raf
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z