905970-84-5Relevant academic research and scientific papers
Lactam-based HDAC inhibitors for anticancer chemotherapy: Restoration of RUNX3 by posttranslational modification and epigenetic control
Cho, Misun,Choi, Eunhyun,Kim, Jae Hyun,Kim, Hwan,Kim, Hwan Mook,Lee, Jang Ik,Hwang, Ki-Chul,Kim, Hyun-Jung,Han, Gyoonhee
, p. 649 - 656 (2014/03/21)
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-activity relationship studies of a series of novel δ-lactam-based histone deacetylase inhibitors
Hwan, Mook Kim,Ryu, Dong-Kyu,Choi, Yongseok,Bum, Woo Park,Lee, Kiho,Sang, Bae Han,Lee, Chang-Woo,Kang, Moo-Rim,Jong, Soon Kang,Boovanahalli, Shanthaveerappa K.,Park, Song-Kyu,Jung, Whan Han,Chun, Tae-Gyu,Lee, Hee-Yoon,Nam, Ky-Youb,Eun, Hyun Choi,Han, Gyoonhee
, p. 2737 - 2741 (2008/02/04)
We synthesized a series of δ-lactam-based HDAC inhibitors that were identified with various degrees of anti-inflammatory and cell growth inhibitory activities. Compounds possessing significant HDAC inhibitory activity exhibited both anti-inflammatory and cell growth inhibitory activities as well as significant tumor growth inhibition in the in vivo tumor xenograft experiments. Besides, these compounds demonstrated antiinflammatory properties in vitro via suppression of the production of the proinflammatory cytokine TNF-α and nitric oxide by LPS-stimulated RAW264.7 cells.
Synthesis, enzymatic inhibition, and cancer cell growth inhibition of novel δ-lactam-based histone deacetylase (HDAC) inhibitors
Kim, Hwan Mook,Lee, Kiho,Park, Bum Woo,Ryu, Dong Kyu,Kim, Kangjeon,Lee, Chang Woo,Park, Song-Kyu,Han, Jung Whan,Lee, Hee Yoon,Lee, Hyun Yong,Han, Gyoonhee
, p. 4068 - 4070 (2007/10/03)
δ-Lactam-based hydroxamic acids, inhibitors of histone deacetylase (HDAC), have been synthesized via ring closure metathesis of key diene intermediates followed by conversion to hydroxamic acid analogues. The hydroxamic acids 12a, 12b, and 17c showed potent inhibitory activity in HDAC enzyme assay. The hydroxamic acid 12b exhibited growth inhibitory activity on five human tumor cell lines, showing good sensitivity on the MDA-MB-231 breast tumor cell.
