Alkyl-substituted N-methylaryl-N'-aryl-4-aminobenzamides: A new series of small molecule inhibitors for Wip1 phosphatase

Autor:	Marco Robello, Hongchao Zheng, Mrinmoy Saha, Kara M. George Rosenker, Subrata Debnath, Jay Prakash Kumar, Harichandra D. Tagad, Sharlyn J. Mazur, Ettore Appella, Daniel H. Appella
Rok vydání:	2022
Předmět:	Pharmacology Protein Phosphatase 2C Organic Chemistry Drug Discovery Phosphoprotein Phosphatases Humans General Medicine Tumor Suppressor Protein p53 Protein Serine-Threonine Kinases Phosphorylation DNA Damage
Zdroj:	European journal of medicinal chemistry. 243
ISSN:	1768-3254
Popis:	The wild-type p53 induced phosphatase 1 (Wip1), a member of the serine/threonine-specific PP2C family, is overexpressed in numerous human cancers. Wip1 dephosphorylates p53 as well as several kinases (such as p38 MAPK, ATM, Chk1, and Chk2) in the DNA damage response pathway that are responsible for maintaining genomic stability and preventing oncogenic transformation. As a result, Wip1 is an attractive target for synthetic inhibitors that could be further developed into therapeutics to treat some cancers. In this study, we report a series of alkyl-substituted N-methylaryl-N'-aryl-4-aminobenzamides and their inhibitory activity of the Wip1 phosphatase. A straightforward synthetic route was developed to synthesize the target compounds from commercially available starting materials. Three different portions (R
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c60af2fe47f5d166bd42937846431f61 https://pubmed.ncbi.nlm.nih.gov/36179402 Zobrazit plný text záznamu Full Text from ScienceDirect