798542-83-3

Upstream product

• 5621-44-3 dimethyl 2-methylenepentanedioate 
• 1382449-63-9 C₁₆H₁₉NO₄ 
• 1382449-34-4 C₁₈H₂₃NO₄ 
• 93633-32-0 5-methoxy-2-methylene-5-oxopentanoic acid 

Relevant academic research and scientific papers

Lactam-based HDAC inhibitors for anticancer chemotherapy: Restoration of RUNX3 by posttranslational modification and epigenetic control

Expression and stability of the tumor suppressor runt-related transcription factora 3 (RUNX3) are regulated by histone deacetylase (HDAC). HDAC inhibition alters epigenetic and posttranslational stability of RUNX3, leading to tumor suppression. However, HDAC inhibitors can nonselectively alter global gene expression through chromatin remodeling. Thus, lactam-based HDAC inhibitors were screened to identify potent protein stabilizers that maintain RUNX3 stability by acetylation. RUNX activity and HDAC inhibition were determined for 111 lactam-based analogues through a cell-based RUNX activation and HDAC inhibition assay. 3-[1-(4-Bromobenzyl)-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-N- hydroxypropanamide (11-8) significantly increased RUNX3 acetylation and stability with relatively low RUNX3 mRNA expression and HDAC inhibitory activity. This compound showed significant antitumor effects, which were stronger than SAHA, in an MKN28 xenograft model. Thus, we propose a novel strategy, in which HDAC inhibitors serve as antitumor chemotherapeutic agents that selectively target epigenetic regulation and protein stability of RUNX3.

Structure and property based design, synthesis and biological evaluation of γ-lactam based HDAC inhibitors: Part II

Histone deacetylases (HDACs) are involved in post-translational modification and epi-genetic expression, and have been the intriguing targets for treatment of cancer. In previous study, we reported synthesis and the biological preliminary results of γ-lactam based HDAC inhibitors. Based on the previous results, smaller γ-lactam core HDAC inhibitors are more active than the corresponding series of larger δ-lactam based analogues and the hydrophobic and bulky cap groups are required for better potency which decreased microsomal stability. Thus, γ-lactam analogues with methoxy, trifluoromethyl groups of ortho-, meta-, para-positions of cap group were prepared and evaluated their biological potency. Among them, trifluoromethyl analogues, which have larger lipophilicity, showed better HDAC inhibitory activity than other analogues. In overall, lipophilicity leads to increase hydrophobic interaction between surface of HDAC active site and HDAC inhibitor, improves HDAC inhibitory activity.

NOVEL 2-OXO-HETEROCYCLIC COMPOUNDS AND THE PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME

The present invention is related to new 2-oxo-cyclic compound the process for preparing them and a pharmaceutical composition comprising the same. The present invention provides a pharmaceutical composition for preventing and treating the inflammatory