1622235-87-3Relevant academic research and scientific papers
Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl- d -aspartate (NMDA) Receptor Antagonist
Gynther, Mikko,Proietti Silvestri, Ilaria,Hansen, Jacob C.,Hansen, Kasper B.,Malm, Tarja,Ishchenko, Yevheniia,Larsen, Younes,Han, Liwei,Kayser, Silke,Auriola, Seppo,Petsalo, Aleksanteri,Nielsen, Birgitte,Pickering, Darryl S.,Bunch, Lennart
, p. 9885 - 9904 (2017)
The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure-activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying biological mechanism was shown to be interference with the lipid signaling pathway, leading to reduced expression of MDR transporters and thereby an increased accumulation of sorafenib in the cancer cells. Interference with lipid signaling pathways by NMDA receptor inhibition is a novel and promising strategy for reversing transporter-mediated chemoresistance in cancer cells.
PYRROLIDINE-2-CARBOXYLIC ACID DERIVATIVES AS IGLUR ANTAGONISTS
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Page/Page column 27; 28, (2014/09/03)
The present invention relates to compounds of Formula (I), combinations and use thereof for disease therapy, or pharmaceutically acceptable salt or solvate thereof, including all tautomers, stereoismers and polymorphs thereof, which are iGlu R inhibitors, and hence are useful in the treatment of psychiatric diseases or neurological disorders or a disease or disorder associated with abnormal activities of iGluR receptors.
