Редактирование: KDM4A (раздел)

==Publications==

{{medline-entry
|title=Structure-Based Discovery of a Selective [[KDM5A]] Inhibitor that Exhibits Anti-Cancer Activity via Inducing Cell Cycle Arrest and Senescence in Breast Cancer Cell Lines.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30650517
|abstract=Breast cancer is the one of the most frequent causes of female cancer mortality. [[KDM5A]], a histone demethylase, can increase the proliferation, metastasis, and drug resistance of cancers, including breast cancer, and is thus an important therapeutic target. In the present work, we performed hierarchical virtual screening towards the [[KDM5A]] catalytic pocket from a chemical library containing 90,000 compounds. Using multiple biochemical methods, the cyclopenta[c]chromen derivative   was identified as the top candidate for [[KDM5A]] demethylase inhibitory activity. Compared with the well-known KDM5 inhibitor CPI-455 ( ),   exhibited higher potency against [[KDM5A]] and much higher selectivity for [[KDM5A]] over both [[KDM4A]] and other KDM5 family members (KDM5B and KDM5C). Additionally, compound   repressed the proliferation of various [[KDM5A]]-overexpressing breast cancer cell lines. Mechanistically,   promoted accumulation of p16 and p27 by blocking [[KDM5A]]-mediated H3K4me3 demethylation, leading to cell cycle arrest and senescence. To date, compound   is the first cyclopenta[c]chromen-based [[KDM5A]] inhibitor reported, and may serve as a novel motif for developing more selective and efficacious pharmacological molecules targeting [[KDM5A]]. In addition, our research provides a possible anti-cancer mechanism of [[KDM5A]] inhibitors and highlights the feasibility and significance of [[KDM5A]] as a therapeutic target for [[KDM5A]]-overexpressing breast cancer.

|keywords=* Jumonji domain
* KDM5A
* breast cancer
* cell cycle arrest
* cell senescence
* histone demethylation
* protein-protein interaction
* virtual screening
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360022
}}