Design, Synthesis, and Biological Evaluation of Dual c-Met/HDAC Inhibitors Bearing 2-Aminopyrimidine Scaffold

Zhang, Qingwei; Xu, Guili; Bao, Ya; Jiao, Min-Ru; Li, Jianqi

doi:10.1055/s-0040-1719162

Cited by 1 publication

(1 citation statement)

References 17 publications

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“…As JNK-specific inhibitors have achieved limited success, multitarget inhibitors may be a novel approach for inhibitor development. 123 For example, Compounds 38 and 39 have simultaneously targeted both JNK3 and p38α kinases, resulting in dual inhibitors with nanomolar activity. 82 In addition, the formation of multitarget inhibitors with kinases such as Raf1 and LRRK2 may also be considered, 84,85…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Design and Discovery of c-Jun N-Terminal Kinase Inhibitors and Their Therapeutic Potential in Human Diseases

et al. 2022

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c-Jun N-terminal kinases (JNKs), members of the mitogen-activated protein kinase (MAPK) family, are encoded by three genes: jnk1, jnk2, and jnk3. JNKs are involved in the pathogenesis and development of many diseases, such as neurodegenerative diseases, inflammation, and cancers. Therefore, JNKs have become important therapeutic targets. Many JNK inhibitors have been discovered, and some have been introduced into clinical trials. However, the study of isoform-selective JNK inhibitors is still a challenging task. To further develop novel JNK inhibitors with clinical value, a comprehensive understanding of JNKs and their corresponding inhibitors is required. In this Perspective, we introduced the JNK signaling pathways and reviewed different chemical types of JNK inhibitors, focusing on their structure–activity relationships and biological activities. The challenges and strategies for the development of JNK inhibitors are also discussed. It is hoped that this Perspective will provide valuable references for the development of novel selective JNK inhibitors.

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