192768-24-4Relevant academic research and scientific papers
Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide
Kankanala, Jayakanth,Ribeiro, Carlos J. A.,Kiselev, Evgeny,Ravji, Azhar,Williams, Jessica,Xie, Jiashu,Aihara, Hideki,Pommier, Yves,Wang, Zhengqiang
supporting information, p. 4669 - 4682 (2019/05/17)
Topoisomerase II (TOP2) poisons as anticancer drugs work by trapping TOP2 cleavage complexes (TOP2cc) to generate DNA damage. Repair of such damage by tyrosyl DNA phosphodiesterase 2 (TDP2) could render cancer cells resistant to TOP2 poisons. Inhibiting TDP2, thus, represents an attractive mechanism-based chemosensitization approach. Currently known TDP2 inhibitors lack cellular potency and/or permeability. We report herein two novel subtypes of the deazaflavin TDP2 inhibitor core. By introducing an additional phenyl ring to the N-10 phenyl ring (subtype 11) or to the N-3 site of the deazaflavin scaffold (subtype 12), we have generated novel analogues with considerably improved biochemical potency and/or permeability. Importantly, many analogues of both subtypes, particularly compounds 11a, 11e, 12a, 12b, and 12h, exhibited much stronger cancer cell sensitizing effect than the best previous analogue 4a toward the treatment with etoposide, suggesting that these analogues could serve as effective cellular probes.
Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling
Li, Zhengqiu,Hao, Piliang,Li, Lin,Tan, Chelsea Y. J.,Cheng, Xiamin,Chen, Grace Y. J.,Sze, Siu Kwan,Shen, Han-Ming,Yao, Shao Q.
supporting information, p. 8551 - 8556 (2013/09/12)
Less is more: A minimalist "clickable" photo-crosslinker (see scheme) was incorporated with numerous small-molecule kinase inhibitors. The resulting probes were used for both in vitro (cell lysates) and in situ (live cells) proteome profiling, for large-scale identification of their potential cellular kinase targets and shows improved outcomes over previous probes. Copyright
Synthesis and antitumor activity of novel diaryl ether hydroxamic acids derivatives as potential HDAC inhibitors
Zhu, Yong,Chen, Xin,Wu, Zeng,Zheng, Yixuan,Chen, Yadong,Tang, Weifang,Lu, Tao
, p. 1723 - 1732 (2013/03/13)
A series of diaryl ether hydroxamic acids were synthesized for the first time and evaluated for the HDAC biology and antiproliferative activity. The structures of these new hydroxamic acids derivatives were confirmed by IR, 1H-NMR and mass spectrum. Some of these compounds showed micro molar activity in the HDAC inhibitory assay and against four cancer cell lines.
Diarylether inhibitors of farnesyl-protein transferase
Dinsmore, Christopher J.,Williams, Theresa M.,Hamilton, Kelly,O'Neill, Timothy J.,Rands, Elaine,Koblan, Kenneth S.,Kohl, Nancy E.,Gibbs, Jackson B.,Graham, Samuel L.,Hartman, George D.,Oliff, Allen I.
, p. 1345 - 1348 (2007/10/03)
The design and synthesis of simple nonpeptide inhibitors of farnesyl-protein transferase (FTase) are described. Cysteine-derived diarylether frameworks are appropriate structural replacements for the C-terminal tetrapeptide portion of the Ras protein, and possess in vitro potency against FTase. Inhibitory activity is dependent on the ring-substitution pattern, and does not require the presence of a C-terminal carboxylate group.
