93475-89-9Relevant academic research and scientific papers
Fragment-based drug discovery of triazole inhibitors to block PDEδ-RAS protein-protein interaction
Chen, Danqi,Chen, Yuehong,Lian, Fulin,Chen, Liu,Li, Yanlian,Cao, Danyan,Wang, Xin,Chen, Lin,Li, Jian,Meng, Tao,Huang, Min,Geng, Meiyu,Shen, Jingkang,Zhang, Naixia,Xiong, Bing
, p. 597 - 609 (2019/01/04)
Although mutated Ras protein is well recognized as an important drug target, direct targeting Ras has proven to be a daunting task. Recent studies demonstrated that Ras protein needs PDEδ to relocate to plasma membrane to execute its signaling transduction function, which provides a new avenue for modulating the Ras protein. To find small molecules antagonizing the interactions between PDEδ and Ras, here we presented a successful application of fragment-based drug discovery of PDEδ inhibitors. Under the guidance of crystal structures, we are able to quickly optimize the initial fragment into highly potent inhibitors, with more than 2000-fold improvement in binding activity, which further adds to the arsenal towards the inhibition of Ras signaling in cancer therapy.
Triazole derivative, preparation method and uses thereof
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, (2019/05/02)
The present invention relates to a PDE inhibitor, particularly to a PDE[delta] inhibitor, specifically to a triazole derivative represented by a general formula (I), a preparation method and uses thereof. According to the present invention, a series of the compounds have good PDE[delta] inhibitory activities, can be used for preparing drugs for treating or preventing KRas-PDE[delta]-mediated diseases, and are particularly suitable for the preparation of KRas-PDE[delta]-mediated antitumor drugs, wherein each substituent in the general formula (I) is the same as the definition of the specification. The formula I is defined in the specification.
