Cereblon-recruiting proteolysis targeting chimeras (PROTACs) can determine the selective degradation of HDAC1 over HDAC3

Author(s)

Pavan, Aline R. ; Smalley, Joshua P. ; Patel, Urvashi ; Pytel, Wiktoria A. ; dos Santos, Jean Leandro ; Cowley, Shaun M. ; Schwabe, John W. R. ; Hodgkinson, James T.

• Document type: Journal article
• Source: CHEMICAL COMMUNICATIONS; v. 60, n. 94, p. 4-pg., 2024-11-05.

Abstract

Histone deacetylase (HDAC) enzymes 1-3 exist in several corepressor complexes and are viable drug targets. To date, proteolysis targeting chimeras (PROTACs) designed to target HDAC1-3 typically exhibit the selective degradation of HDAC3. Herein, we report cereblon-recruiting PROTACs that degrade HDAC1 with selectivity over HDAC3. (AU)

• FAPESP's process: 21/10059-9 - Synthesis and pharmacological evaluation of PROTAC-HDAC inhibitors-based compounds for sickle cell disease
• Grantee: Aline Renata Pavan
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 23/05739-6 - Strategies for intervention in gamma-globin gene repressor complexes containing Histone Deacetylase (HDAC-1 and HDAC-2) using small molecules
• Grantee: Jean Leandro dos Santos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/19523-7 - Design, synthesis and pharmacological evaluation of hydroxyurea derivatives designed as histone deacetylase inhibitors for Sickle Cell Anemia
• Grantee: Aline Renata Pavan
• Support Opportunities: Scholarships in Brazil - Doctorate