798542-77-5

Basic information

• Product Name: N-hydroxy-3-(2-oxo-1-phenethyl-2,5-dihydro-1H-pyrrol-3-yl)-propionamide
• Synonyms: N-hydroxy-3-(2-oxo-1-phenethyl-2,5-dihydro-1H-pyrrol-3-yl)-propionamide
• CAS NO: 798542-77-5
• Molecular Weight: 274.32
• Mol File: 798542-77-5.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: N-hydroxy-3-(2-oxo-1-phenethyl-2,5-dihydro-1H-pyrrol-3-yl)-propionamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-hydroxy-3-(2-oxo-1-phenethyl-2,5-dihydro-1H-pyrrol-3-yl)-propionamide(798542-77-5)
• EPA Substance Registry System: N-hydroxy-3-(2-oxo-1-phenethyl-2,5-dihydro-1H-pyrrol-3-yl)-propionamide(798542-77-5)

Safety Data

• Hazardous Substances Data: 798542-77-5(Hazardous Substances Data)

Upstream product

• 5621-44-3 dimethyl 2-methylenepentanedioate 
• 64-04-0 phenethylamine 
• 5263-58-1 N-allylphenethylamine 
• 1276126-48-7 C₁₆H₁₉NO₃ 
• 1276126-38-5 C₁₈H₂₃NO₃ 
• 93633-32-0 5-methoxy-2-methylene-5-oxopentanoic acid 

Relevant articles and documents

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

Histone deacetylases (HDACs) are involved in post-translational modification and gene expression. Cancer cells recruited amounts of HDACs for their survival by epi-genetic down regulation of tumor suppressor genes. HDACs have been the promising targets for treatment of cancer, and many HDAC inhibitors have been investigated nowadays. In previous study, we synthesized δ-lactam core HDAC inhibitors which showed potent HDAC inhibitory activities as well as cancer cell growth inhibitory activities. Through QSAR study of the δ-lactam based inhibitors, the smaller core is suggested as more active than larger one because it fits better in narrow hydrophobic tunnel of the active pocket of HDAC enzyme. The smaller γ-lactam core HDAC inhibitors were designed and synthesized for biological and property optimization. Phenyl, naphthyl and thiophenyl groups were introduced as the cap groups. Hydrophobic and bulky cap groups increase potency of HDAC inhibition because of hydrophobic interaction between HDAC and inhibitors. In overall, γ-lactam based HDAC inhibitors showed more potent than δ-lactam analogues.