Arylurea Derivatives: A Class of Potential Cancer Targeting Agents

Title:Arylurea Derivatives: A Class of Potential Cancer Targeting Agents

Volume: 17 Issue: 28

Author(s): Jia-Nian Chen*, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou*, Shi-Ming Pu and Wan-Hua Lin

Affiliation:

• State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi,China

• Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi,China

Keywords: Arylurea, Anti-cancer, Signaling pathway inhibitor, Tumor angiogenesis inhibitor, Tumor migration and invasion inhibitor, Structure-activity relationship.

Abstract: Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include Vascular Endothelial Growth Factor Receptors (VEGFRs), Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs), Epidermal Growth Factor Receptors (EGFRs), Insulin-Like Growth Factor 1 Receptor (IGF-1R), Fmslike Tyrosine Kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include Checkpoint Kinases (Chks), Cyclin- Dependent Kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include Matrix Metalloproteinases (MMPs), LIM kinase (Limk), Nicotinamide Phosphoribosyltransferase (Nampt), and Histone Deacetylase (HDAC); (6) arylureas from the rational modification of natural products. This review focuses on the Structure-Activity Relationships (SARs) of these arylureas. The structural evolution and current status of some typical anti-cancer agents used in clinic and/or in clinical trials are emphasized.

Cite this article as:

Chen Jia-Nian *, Wu De-Wen, Li Ting , Yang Kang-Jian, Cheng Li , Zhou Zu-Ping*, Pu Shi-Ming and Lin Wan-Hua, Arylurea Derivatives: A Class of Potential Cancer Targeting Agents, Current Topics in Medicinal Chemistry 2017; 17 (28) . https://dx.doi.org/10.2174/1568026617666170707123553