1453835-27-2Relevant academic research and scientific papers
Discovery of Potent and Selective CDK9 Degraders for Targeting Transcription Regulation in Triple-Negative Breast Cancer
Wei, Dan,Wang, Hanlin,Zeng, Qinghe,Wang, Wenjing,Hao, Bingbing,Feng, Xule,Wang, Peipei,Song, Ning,Kan, Weijuan,Huang, Guifang,Zhou, Xiaoyu,Tan, Minjia,Zhou, Yubo,Huang, Ruimin,Li, Jia,Chen, Xiao-Hua
, p. 14822 - 14847 (2021/10/12)
Triple-negative breast cancer (TNBC) is highly aggressive with very limited treatment options due to the lack of efficient targeted therapies and thus still remains clinically challenging. Targeting transcription-associated cyclin-dependent kinases to remodel transcriptional regulation shows great promise in cancer therapy. Herein, we report the synthesis, optimization, and evaluation of new series of heterobifunctional molecules as highly selective and efficacious CDK9 degraders, enabling potent inhibition of TNBC cell growth and rapidly targeted degradation of CDK9. Moreover, the most potent CDK9 degrader (compound 45) induces cell apoptosis in vitro and inhibits tumor growth in the MDA-MB-231 TNBC model. Furthermore, the RNA-seq, immunohistochemistry assays demonstrate that the CDK9 degrader downregulates the downstream targets, such as MYC, at the transcriptional level, resulting apoptosis in TNBC cells. Our work establishes that 45 is a highly potent and efficacious CDK9 degrader for targeting transcription regulation, which represents an effective strategy and great potential as a new targeted therapy for TNBC.
Pyrazolo-triazine derivatives as selective cyclin-dependent kinase inhinitors
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Paragraph 0263; 0264, (2013/09/12)
The present invention relates to pyrazolo[1,5-a][1,3,5]triazine derivatives and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the prophylaxis and/or treatment of infectious diseases, including opportunistic diseases, immunological diseases, autoimmune diseases, cardiovascular diseases, cell proliferative diseases, inflammation, erectile dysfunction and stroke, and pharmaceutical compositions containing at least one of said pyrazolo[1,5-a][1,3,5]triazine derivatives and/or pharmaceutically acceptable salts thereof. Furthermore, the present invention relates to the use of said pyrazolo[1,5-a][1,3,5]triazine derivatives as inhibitors for a protein kinase.
PYRAZOLO - TRIAZINE DERIVATIVES AS SELECTIVE CYCLIN- DEPENDENT KINASE INHINITORS
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Page/Page column 149; 150, (2013/09/12)
The present invention relates to pyrazolo[1,5-a][1,3,5]triazine derivatives and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the prophylaxis and/or treatment of infectious diseases, including opportunistic diseases, immunological diseases, autoimmune diseases, cardiovascular diseases, cell proliferative diseases, inflammation, erectile dysfunction and stroke, and pharmaceutical compositions containing at least one of said pyrazolo[1,5-a][1,3,5]triazine derivatives and/or pharmaceutically acceptable salts thereof. Furthermore, the present invention relates to the use of said pyrazolo[1,5-a][1,3,5]triazine derivatives as inhibitors for a protein kinase.
