28948-60-9Relevant articles and documents
Synthesis and evaluation of bifunctional PTP4A3 phosphatase inhibitors activating the ER stress pathway
Brodsky, Jeffrey L.,Hart, Duncan J.,Lazo, John S.,Rastelli, Ettore J.,Sannino, Sara,Sharlow, Elizabeth R.,Wipf, Peter
, (2021/06/21)
We developed JMS-053, a potent inhibitor of the dual specificity phosphatase PTP4A3 that is potentially suitable for cancer therapy. Due to the emerging role of the unfolded protein response (UPR) in cancer pathology, we sought to identify derivatives that combine PTP4A3 inhibition with induction of endoplasmatic reticulum (ER) stress, with the goal to generate more potent anticancer agents. We have now generated bifunctional analogs that link the JMS-053 pharmacophore to an adamantyl moiety and act in concert with the phosphatase inhibitor to induce ER stress and cell death. The most potent compound in this series, 7a, demonstrated a ca. 5-fold increase in cytotoxicity in a breast cancer cell line and strong activation of UPR and ER stress response genes in spite of a ca. 13-fold decrease in PTP4A3 inhibition. These results demonstrate that the combination of phosphatase inhibition with UPR/ER-stress upregulation potentiates efficacy.
BENZAZEPINE DERIVATIVE, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
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Paragraph 0153; 0164; 0165, (2019/03/29)
Disclosed are a benzazepine derivative, a preparation method, a pharmaceutical composition and the use thereof. A compound as shown in formula (I) of the present invention, and an isomer, a prodrug, a stable isotope derivative or a pharmaceutically acceptable salt thereof have the following structure. The benzazepine derivative of the present invention has a good regulation effect on the TLR family and the related signalling pathway, and in particular, has a good regulation effect on TLR8, can effectively treat, relieve and/or prevent various diseases mediated by TLR family and the TLR-related signalling pathway, and in particular, can effectively treat, relieve and/or prevent various diseases mediated by TLR8, such as cancers, autoimmune diseases, infections, inflammations, transplantation rejections, graft-versus-host diseases, etc.
Identification of 2-(4-pyridyl)thienopyridinones as GSK-3β inhibitors
Gentile, Gabriella,Bernasconi, Giovanni,Pozzan, Alfonso,Merlo, Giancarlo,Marzorati, Paola,Bamborough, Paul,Bax, Benjamin,Bridges, Angela,Brough, Caroline,Carter, Paul,Cutler, Geoffrey,Neu, Margarete,Takada, Mia
, p. 4823 - 4827 (2011/09/21)
The discovery of a novel series of 2-(4-pyridyl)thienopyridinone GSK-3β inhibitors is reported. X-ray crystallography reveals its binding mode and enables rationalization of the SAR. The initial optimization of the template for improved cellular activity and predicted CNS penetration is also presented.