3398-16-1Relevant articles and documents
Tumor microenvironment and NIR laser dual-responsive release of berberine 9-: O -pyrazole alkyl derivative loaded in graphene oxide nanosheets for chemo-photothermal synergetic cancer therapy
Cai, Shundong,Du, Peifang,Liu, Yanfei,Liu, Zhenbao,Long, Shuo,Peng, Dongming,Wang, Yirong,Wen, Nachuan,Xiong, Hongjie,Yan, Jianhua
, p. 4046 - 4055 (2020)
A berberine 9-O-pyrazole alkyl derivative, a chemical compound (called B3) previously synthesized by our group, shows anti-cancer activity. However, B3 lacks targeting cytotoxicity to cancer cells, leading to obvious toxic side effects on normal cells. To solve this problem, here, we prepared a drug delivery system, namely, AS1411-GO/B3 for tumor targeting, in which nano-graphene oxide (GO) sheets were employed as the drug carrier, and the aptamer AS1411 was conjugated onto GO for tumor targeting. GO also had a photothermal effect, which helped the release of B3 from GO as well as the thermal cytotoxicity to cells. We found that the release of B3 could respond to acid conditions, indicating that the tumor intracellular environment could promote the release of B3, thus allowing it to perform chemotherapy effects. This system could also release B3 in response to photothermal heating, moreover, combined photothermal therapy and chemotherapy to improve the anticancer activity was achieved. This AS1411-GO/B3 platform with chemo-photothermal synergetic therapy provides a very promising treatment for tumors.
Identification of Isoform 2 Acid-Sensing Ion Channel Inhibitors as Tool Compounds for Target Validation Studies in CNS
Bencheva, Leda Ivanova,De Matteo, Marilenia,Ferrante, Luca,Ferrara, Marco,Prandi, Adolfo,Randazzo, Pietro,Ronzoni, Silvano,Sinisi, Roberta,Seneci, Pierfausto,Summa, Vincenzo,Gallo, Mariana,Veneziano, Maria,Cellucci, Antonella,Mazzocchi, Nausicaa,Menegon, Andrea,Di Fabio, Romano
supporting information, p. 627 - 632 (2019/03/07)
Acid-sensing ion channels (ASICs) are a family of ion channels permeable to cations and largely responsible for the onset of acid-evoked ion currents both in neurons and in different types of cancer cells, thus representing a potential target for drug discovery. Owing to the limited attention ASIC2 has received so far, an exploratory program was initiated to identify ASIC2 inhibitors using diminazene, a known pan-ASIC inhibitor, as a chemical starting point for structural elaboration. The performed exploration enabled the identification of a novel series of ASIC2 inhibitors. In particular, compound 2u is a brain penetrant ASIC2 inhibitor endowed with an optimal pharmacokinetic profile. This compound may represent a useful tool to validate in animal models in vivo the role of ASIC2 in different neurodegenerative central nervous system pathologies.
Discovery of DS79182026: A potent orally active hepcidin production inhibitor
Fukuda, Takeshi,Goto, Riki,Kiho, Toshihiro,Ueda, Kenjiro,Muramatsu, Sumie,Hashimoto, Masami,Aki, Anri,Watanabe, Kengo,Tanaka, Naoki
, p. 3716 - 3722 (2017/07/27)
Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. Inhibition of hepcidin could be a strategy favorable to treating anemia of chronic disease (ACD). We report herein the synthesis and structure-activity relationships (SARs) of a series of benzisoxazole compounds as orally active hepcidin production inhibitors. The optimization study of multi kinase inhibitor 1 led to a potent and bioavailable hepcidin production inhibitor 38 (DS79182026), which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model.