959239-07-7Relevant academic research and scientific papers
Development of Multifunctional Histone Deacetylase 6 Degraders with Potent Antimyeloma Activity
Wu, Hao,Yang, Ka,Zhang, Zhongrui,Leisten, Eric D.,Li, Ziyuan,Xie, Haibo,Liu, Jin,Smith, Kerry A.,Novakova, Zora,Barinka, Cyril,Tang, Weiping
, p. 7042 - 7057 (2019)
Histone deacetylase 6 (HDAC6) primarily catalyzes the removal of acetyl group from the side chain of acetylated lysine residues in cytoplasmic proteins such as α-tubulin and HSP90. HDAC6 is involved in multiple disease-relevant pathways. Based on the proteolysis targeting chimera strategy, we previously developed the first HDAC6 degrader by tethering a pan-HDAC inhibitor with cereblon (CRBN) E3 ubiquitin ligase ligand. We herein report our new generation of multifunctional HDAC6 degraders by tethering selective HDAC6 inhibitor Nexturastat A with CRBN ligand that can synergize with HDAC6 degradation for the antiproliferation of multiple myeloma (MM). This new class of degraders exhibited improved potency and selectivity for the degradation of HDAC6. After the optimization of the linker length and linking positions, we discovered potent HDAC6 degraders with nanomolar DC50 and promising antiproliferation activity in multiple myeloma (MM) cells.
SYNTHESIS OF SMALL MOLECULE HISTONE DEACETYLASE 6 DEGRADERS, COMPOUNDS FORMED THEREBY, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Paragraph 0078; 0104; 0165; 0173, (2020/02/10)
Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.
AMIDINE SUBSTITUTED BETA - LACTAM COMPOUNDS, THEIR PREPARATION AND USE AS ANTIBACTERIAL AGENTS
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Paragraph 00162; 00163, (2013/08/15)
The present invention relates to novel β-lactam compounds of formula (I), their preparation and use. In particular, this invention relates to novel β-lactam compounds which are amidine substituted monobactam derivatives useful as antimicrobial agents and their preparation.
