7022-37-9Relevant articles and documents
Novel small molecular compound ae-848 potently induces human multiple myeloma cell apoptosis by modulating the nf-κb and pi3k/ akt/mtor signaling pathways
Xu, Yaqi,Feng, Xiaoli,Zhou, Qian,Jiang, Wen,Dai, Yibo,Jiang, Yang,Liu, Xiaoli,Li, Shuo,Wang, Yongjing,Wang, Fang,Li, Ai,Zheng, Chengyun
, p. 13063 - 13075 (2021/01/11)
Background: We aimed to investigate the anti-multiple myeloma (MM) activity of the new small molecular compound AE-848 (5-bromo-2-hydroxyisophthalaldehyde bis[(1-methyl-1H-benzimidazol-2-yl)hydrazone]) and its underlying anti-MM mechanism. Methods: Cell viability and apoptosis were detected and quantified by using MTT and flow cytometry, respectively. JC-1 dye-related techniques were used to assess mitochondrial membrane potential (MMP). Western blotting was applied to detect the expression of NF-κB and PI3K/Akt/mTOR pathway-associated proteins. The in vivo activity of AE-848 against MM was evaluated in a MM mouse model. Results: Application of AE-848 into the in vitro cell culture system significantly reduced the viability and induced apoptosis of the MM cell lines, RPMI-8226 and U266, in a dose-and time-dependent manner, respectively. JC-1 dye and Western blotting analysis revealed that AE-848 induced the cleavage of caspase-8, caspase-3, and poly ADP-ribose polymerase (PARP), resulting in loss of mitochondrial membrane potential (MMP). Both the NF-κB and PI3K/AKT/mTOR signaling pathways were involved in AE-848-induced apoptosis of U266 and RPMI8226 cells. Moreover, AE-848 leads to cell cycle arrest of MM cells. Its anti-MM efficacy was further confirmed in a xenograft model of MM. AE-848 administration significantly inhibited MM tumor progression and prolonged the survival of MM-bearing mice. More importantly, our results demonstrated that AE-848 markedly induced primary MM cell apoptosis. Conclusion: Our results for the first time showed that the small compound AE-848 had potent in vitro and in vivo anti-myeloma activity, indicating that AE-848 may have great potential to be developed as a drug for MM treatment.
Antitumor compound, method for synthesizing same and application of antitumor compound
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Paragraph 0018, (2018/10/19)
The invention provides an antitumor compound. A chemical name of the antitumor compound is 5-bromine-2-hydroxyl isophthalaldehyde di-[(1-methyl-1H-benzimidazole-2-group) hydrazone]. The antitumor compound which is an antitumor medicine can be used for pre
Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs
Nakao, Syuhei,Mabuchi, Miyuki,Shimizu, Tadashi,Itoh, Yoshihiro,Takeuchi, Yuko,Ueda, Masahiro,Mizuno, Hiroaki,Shigi, Naoko,Ohshio, Ikumi,Jinguji, Kentaro,Ueda, Yuko,Yamamoto, Masatatsu,Furukawa, Tatsuhiko,Aoki, Shunji,Tsujikawa, Kazutake,Tanaka, Akito
, p. 1071 - 1074 (2014/03/21)
A series of 1-aryl-3,4-substituted-1H-pyrazol-5-ol derivatives was synthesized and evaluated as prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors to obtain a novel anti-prostate cancer drug. After modifying 1-(1H-benzimidazol-2-yl)-3,4-dimethyl-1H-pyrazol-5-ol (1), a hit compound found during random screening using a recombinant PCA-1/ALKBH3, 1-(1H-5- methylbenzimidazol-2-yl)-4-benzyl-3-methyl-1H-pyrazol-5-ol (35, HUHS015), was obtained as a potent PCA-1/ALKBH3 inhibitor both in vitro and in vivo. The bioavailability (BA) of 35 was 7.2% in rats after oral administration. As expected, continuously administering 35 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects.
