51224-89-6Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents
Dai, Qiuzi,Chen, Jiwei,Gao, Chunmei,Sun, Qinsheng,Yuan, Zigao,Jiang, Yuyang
, p. 404 - 408 (2019/06/24)
In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10 mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.
Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B
Liu, Gang,Szczepankiewicz, Bruce G.,Pei, Zhonghua,Janowick, David A.,Xin, Zhili,Hajduk, Philip J.,Abad-Zapatero, Cele,Liang, Heng,Hutchins, Charles W.,Fesik, Stephen W.,Ballaron, Steve J.,Stashko, Mike A.,Lubben, Tom,Mika, Amanda K.,Zinker, Bradley A.,Trevillyan, James M.,Jirousek, Michael R.
, p. 2093 - 2103 (2007/10/03)
Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.
