38426-11-8Relevant articles and documents
Lead Optimization and Structure-Activity Relationship Studies on Myeloid Ecotropic Viral Integration Site 1 Inhibitor
Turgutalp, Bengisu,Uslu, Merve,Helvacioglu, Sinem,Charehsaz, Mohammad,Gurdal, Enise Ece,Sippl, Wolfgang,Kocabas, Fatih,Yarim, Mine
, p. 14448 - 14464 (2021/10/12)
The pivotal role of the myeloid ecotropic viral integration site 1 (MEIS1) transcriptional factor was reported in cardiac regeneration and hematopoietic stem-cell (HSC) regulation with our previous findings. MEIS1 as a promising target in the context of p
Discovery of 4 H-Chromen-4-one Derivatives as a New Class of Selective Rho Kinase (ROCK) Inhibitors, which Showed Potent Activity in ex Vivo Diabetic Retinopathy Models
Zhao, Lanying,Li, Yueshan,Wang, Yujiao,Qiao, Zeen,Miao, Zhuang,Yang, Jiao,Huang, Luyi,Tian, Chenyu,Li, Linli,Chen, Danian,Yang, Shengyong
, p. 10691 - 10710 (2019/11/28)
Diabetic retinopathy (DR) is a major cause of blindness, and there is a lack of effective treatment at present. Rho-associated coiled-coil containing serine/threonine protein kinases (ROCKs) have recently been suggested as potential targets for the DR treatment. We herein report the discovery of 4H-chromen-4-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship analyses led to the identification of the most active compound, 4-(dimethylamino)-N-(3-{2-[(4-oxo-4H-chromen-7-yl)oxy]acetamido}phenyl) (12j). This compound showed excellent kinase selectivity for ROCK I and ROCK II against 387 other kinases. In retinal explants, compound 12j protected retinal neurons from high glucose-induced oxidative stress and apoptosis-mediated cell death. Furthermore, 12j administration suppressed the improper proliferation of Müller cells and promoted the regression of vascular vessels in retinal explants cultured in a high glucose microenvironment. Collectively, our data suggest that 12j could be a potential lead compound for the treatment of DR, hence deserving further in-depth studies.
Discovery of novel inhibitors of signal transducer and activator of transcription 3 (STAT3) signaling pathway by virtual screening
Zhang, Mingming,Zhu, Weiliang,Li, Yingxia
, p. 301 - 310 (2013/05/22)
Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway has been considered a novel therapeutic strategy to treat human cancers that harbor aberrantly-active STAT3. In this study, nearly 204,000 compounds in Specs database were screened by virtual screening, and samples of top 100 compounds identified as candidate small-molecule inhibitors of STAT3 were evaluated by STAT3-dependent luciferase reporter assay as well as other cell-based assays. A benzothiazole core scaffold containing compound, 9, was identified as an inhibitor of IL-6/STAT3 signaling with an IC50 of 3.567 μM. It is the first time to discover benzothiazole scaffold as a potent STAT3 signaling inhibitor. We further investigated the (structure-activity relationship) SAR of the benzothiazole analogues, and discovered compound 16w as a better small-molecule inhibitor. Both compounds inhibited the phosphorylation of STAT3 and had no obvious effect on upstream JAK2 kinase.
Tricycloundecane compounds useful as modulators of nuclear hormone receptor function
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Page/Page column 47, (2008/06/13)
Tricycloundecanes compounds, methods of using such compounds in the treatment of nuclear hormone receptor-associated conditions such as cancer and immune disorders, and pharmaceutical compositions containing such compounds are disclosed.
