Fang, Zhen; Liu, Yang; Zhang, Rong; Chen, Qiang; Wang, Tianqi; Yang, Wei; Fan, Yan; Yu, Chundong; Xiang, Rong; Yang, Shengyong published the artcile< Discovery of a potent and selective inhibitor of histone lysine demethylase KDM4D>, COA of Formula: C10H7NOS, the main research area is histone lysine demethylase KDM4D inhibitor arylpyrrolidinmethylphenol; 2-OG noncompetitive Inhibitor; Epigenetics; KDM4D; Structure-activity relationship.
Histone lysine demethylase 4D (KDM4D) plays an important role in the regulation of tumorigenesis, progression and drug resistance and has been considered a potential target for cancer treatment. However, there is still a lack of potent and selective KDM4D inhibitors. In this investigation, we report a new class of KDM4D inhibitors containing the 2-(aryl(pyrrolidine-1-yl)methyl)phenol scaffold, identified through AlphaLisa-based screening, structural optimization, and structure-activity relationship analyses. Among these inhibitors, 24s (I) was the most potent, with an IC50 value of 0.023 ± 0.004μM. This compound exhibited more than 1500-fold selectivity towards KDM4D vs. KDM4A as well as other JMJD subfamily members, indicating good selectivity for KDM4D. Kinetic anal. indicated that 24s did not occupy the 2-oxoglutarate binding pocket. In an in vitro assay, 24s significantly suppressed the proliferation and migration of colorectal cancer (CRC) cells. Overall, this study has identified a good tool compound to explore the biol. function of KDM4D and a good lead compound for drug discovery targeting KDM4D.
European Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, COA of Formula: C10H7NOS.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica