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Review Article Open Access
Volume 2 | Issue 3 | DOI: https://doi.org/10.33696/Signaling.2.051

Targeting Cullin-RING E3 Ubiquitin Ligase 4 by Small Molecule Modulators

  • 1Department of Oncological Sciences, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029-6574, USA
  • 2Genetics and Genomics, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029-6574,USA
  • 3Department of Pharmacological Sciences, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029-6574, USA
  • 4Drug Discovery Institute, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029-6574, USA
+ Affiliations - Affiliations

Corresponding Author

Zhen-Qiang Pan, zhen-qiang.pan@mssm.edu

Received Date: July 19, 2021

Accepted Date: September 07, 2021

Abstract

Cullin-RING E3 ubiquitin ligase 4 (CRL4) plays an essential role in cell cycle progression. Recent efforts using high throughput screening and follow up hit-to-lead studies have led to identification of small molecules 33-11 and KH-4-43 that inhibit E3 CRL4’s core ligase complex and exhibit anticancer potential. This review provides: 1) an updated perspective of E3 CRL4, including structural organization, major substrate targets and role in cancer; 2) a discussion of the challenges and strategies for finding the CRL inhibitor; and 3) a summary of the properties of the identified CRL4 inhibitors as well as a perspective on their potential utility to probe CRL4 biology and act as therapeutic agents.

Keywords

E3 CRL4, Cdt1, Cell cycle, Small molecule inhibitors, Tumor inhibition

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