ZYH005, a novel DNA intercalator, overcomes all-trans retinoic acid resistance in acute promyelocytic leukemia was written by Tong, Qingyi;You, Huijuan;Chen, Xintao;Wang, Kongchao;Sun, Weiguang;Pei, Yufeng;Zhao, Xiaodan;Yuan, Ming;Zhu, Hucheng;Luo, Zengwei;Zhang, Yonghui. And the article was included in Nucleic Acids Research in 2018.Related Products of 14425-64-0 This article mentions the following:
Despite All-trans retinoic acid (ATRA) has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematol. cancer, there remains a clin. challenge that many high-risk APL patients who fail to achieve a complete mol. remission or relapse and become resistant to ATRA. Herein, we report that 5-(4-methoxyphenethyl)-[1, 3] dioxolo [4, 5- j] phenanthridin-6(5H)-one (ZYH005) exhibits specific anticancer effects on APL and ATRA-resistant APL in vitro and vivo, while shows negligible cytotoxic effect on non-cancerous cell lines and peripheral blood mononuclear cells from healthy donors. Using single-mol. magnetic tweezers and mol. docking, we demonstrate that ZYH005 is a DNA intercalator. Further mechanistic studies show that ZYH005 triggers DNA damage, and caspase-dependent degradation of the PML-RARa fusion protein. As a result, APL and ATRA-resistant APL cells underwent apoptosis upon ZYH005 treatment and this apoptosis-inducing effect is even stronger than that of arsenic trioxide and anticancer agents including 5-fluorouracil, cisplatin and doxorubicin. Moreover, ZYH005 represses leukemia development in vivo and prolongs the survival of both APL and ATRA-resistant APL mice. To our knowledge, ZYH005 is the first synthetic phenanthridinone derivative, which functions as a DNA intercalator and can serve as a potential candidate drug for APL, particularly for ATRA-resistant APL. In the experiment, the researchers used many compounds, for example, 1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0Related Products of 14425-64-0).
1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact. When the molecular ion is detected, the bromine and chlorine isotope patterns are very distinct, but caution is to be exercised for certain mixed chlorinated/brominated compounds, which can look similar to homohalogen patterns.Related Products of 14425-64-0
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary