Synthesis and Evaluation of a Class of Compounds Inhibiting the Growth of Stromal Antigen 2 ( STAG2 )‐Mutant Ewing Sarcoma Cells

Autor:	Nenggang Zhang, Keng‐Fu Lin, Christian Yang, Scott Peruski, Debananda Pati, Scott R. Gilbertson
Rok vydání:	2022
Předmět:	Pharmacology Cell Line Tumor Mutation Organic Chemistry Drug Discovery Humans Molecular Medicine Cell Cycle Proteins Sarcoma Ewing General Pharmacology Toxicology and Pharmaceutics Biochemistry
Zdroj:	ChemMedChem. 17
ISSN:	1860-7187 1860-7179
DOI:	10.1002/cmdc.202100653
Popis:	STAG2 (SA2) is a critical component of the cohesin complex that regulates gene expression and the separation of sister chromatids in cells. Mutations in STAG2 have been identified in over thirty different types of cancers including myeloid leukaemia, non-small cell lung, bladder and Ewing sarcoma. Selectively inhibiting cancer cells lacking of STAG2 is an attractive approach for the cancer therapy. Here we report that a small molecule, StagX1, identified through a high-throughput screening, inhibits the growth of Ewing sarcoma cells possessing mutant STAG2. A new synthetic route to the StagX1 scaffold and new versions of the molecule along with their activity in a cell viability assay are reported.
Databáze:	OpenAIRE
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