40751-88-0Relevant articles and documents
COMPOUNDS AND METHODS FOR INHIBITING VIRAL REPLICATION AND METHODS OF TREATING AND PREVENTING FLAVIVIRAL INFECTIONS
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, (2022/02/05)
The present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. The present disclosure further relates to methods of inhibiting viral replication including contacting one or more cells that have been infected wit
AMIDE-SUBSTITUTED HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF CONDITIONS RELATED TO THE MODULATION OF IL-12, IL-23 AND/OR IFN-ALPHA
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Page/Page column 94, (2020/05/29)
Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-2
Drug Design Targeting T-Cell Factor-Driven Epithelial-Mesenchymal Transition as a Therapeutic Strategy for Colorectal Cancer
Abraham, Adedoyin D.,Esquer, Hector,Zhou, Qiong,Tomlinson, Nicholas,Hamill, Brayden D.,Abbott, Joshua M.,Li, Linfeng,Pike, Laura A.,Rinaldetti, Sébastien,Ramirez, Dominique A.,Lunghofer, Paul J.,Gomez, Jose D.,Schaack, Jerome,Nemkov, Travis,D'Alessandro, Angelo,Hansen, Kirk C.,Gustafson, Daniel L.,Messersmith, Wells A.,Labarbera, Daniel V.
supporting information, p. 10182 - 10203 (2019/11/29)
Metastasis is the cause of 90% of mortality in cancer patients. For metastatic colorectal cancer (mCRC), the standard-of-care drug therapies only palliate the symptoms but are ineffective, evidenced by a low survival rate of ~11%. T-cell factor (TCF) transcription is a major driving force in CRC, and we have characterized it to be a master regulator of epithelial-mesenchymal transition (EMT). EMT transforms relatively benign epithelial tumor cells into quasi-mesenchymal or mesenchymal cells that possess cancer stem cell properties, promoting multidrug resistance and metastasis. We have identified topoisomerase IIα (TOP2A) as a DNA-binding factor required for TCF-transcription. Herein, we describe the design, synthesis, biological evaluation, and in vitro and in vivo pharmacokinetic analysis of TOP2A ATP-competitive inhibitors that prevent TCF-transcription and modulate or reverse EMT in mCRC. Unlike TOP2A poisons, ATP-competitive inhibitors do not damage DNA, potentially limiting adverse effects. This work demonstrates a new therapeutic strategy targeting TOP2A for the treatment of mCRC and potentially other types of cancers.