Optimization of Class I Histone Deacetylase PROTACs Reveals thatHDAC1/2 Degradation is Critical to Induce Apoptosis and Cell Arrest in Cancer Cells

• Published in: Journal of medicinal chemistry Vol. 65; no. 7; pp. 5642 - 5659
• Main Authors: Smalley, Joshua P., Baker, India M., Pytel, Wiktoria A., Lin, Li-Ying, Bowman, Karen J., Schwabe, John W. R., Cowley, Shaun M., Hodgkinson, James T.
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 14.04.2022
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; POTENT; GENE; HDAC1; CHEMICAL PROBE; INHIBITORS; DISCOVERY

Class I histone deacetylase (HDAC) enzymes 1, 2, and 3 organize chromatin as the catalytic subunits within seven distinct multiprotein corepressorcomplexes and are established drug targets. We report optimization studies ofbenzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chime...