Luo, Guoshun; Lin, Xin; Ren, Shengnan; Wu, Shuangjie; Wang, Xin; Ma, Luyu; Xiang, Hua published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Development of novel tetrahydroisoquinoline-hydroxamate conjugates as potent dual SERDs/HDAC inhibitors for the treatment of breast cancer》.Category: bromides-buliding-blocks The article contains the following contents:
Concomitant inhibition of estrogen receptor alpha (ERα) and histone deacetylase (HDAC) signaling has been proven effective in endocrine-resistant ER+ breast cancers. Herein, a series of tetrahydroisoquinoline (THIQ)-hydroxamate conjugates were rationally designed and synthesized as dual SERDs/HDAC inhibitors by incorporating the hydroxamate, a known HDAC pharmacophore, into a privileged THIQ scaffold of selective ERα degraders (SERDs). Some of these THIQ-hydroxamate conjugates displayed remarkable HDAC6 inhibition and improved antiproliferative activity against MCF-7 cells. Particularly, the most potent HDAC inhibitor 19k also exhibits potent ERα binding affinity, good ERα degradation efficacy and the best antiproliferative activity. Besides, 19k displayed superior antitumor efficacy than the drug combination (Fulvestrant + SAHA) through promoting ERα degradation and histone acetylation in an MCF-7 xenograft model, without causing observable toxicity. Collectively, this study validates the therapeutic potential of a dual-acting compound with potent ERα degradation efficacy and HDAC6 inhibition in breast cancer. In the part of experimental materials, we found many familiar compounds, such as Ethyl 3-bromopropanoate(cas: 539-74-2Category: bromides-buliding-blocks)
Ethyl 3-bromopropanoate(cas: 539-74-2) belongs to organobromine compounds.Depending on the type of carbon to which the bromine is bonded, organic bromide could be alkyl, alkenyl, alkynyl, or aryl. Dehydrobromination, Grignard reactions, reductive coupling, Wittig reaction, and several nucleophilic substitution reactions are some of the principal reactions which involve organic bromides. Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary