We identified a new benzothiophene containing Rho kinase inhibitor scaffold in an ultra high-throughput enzymatic activity screen. SAR studies, driven by a novel label-free cellular impedance assay, were used to derive 39, which substantially reduced intraocular pressure in a monkey model of glaucoma-associated ocular hypertension.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2010.04.020 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovery of the First-in-Class Dual-Target ROCK/HDAC Inhibitor with Potent Antitumor Efficacy in Vivo That Trigger Antitumor Immunity.
J Med Chem
November 2024
Institute of Marine Biology and Pharmacology, Ocean College, Zhejiang University, Zhoushan 316021, China.
Triple-negative breast cancer (TNBC) represents a highly aggressive and heterogeneous malignancy. Currently, multitarget drug approaches present a promising therapeutic approach for TNBC. Utilizing a combinatorial chemistry strategy to construct a virtual screening database, dual ROCK/HDAC-targeting benzothiophene compounds were identified.
View Article and Find Full Text PDFActivation of mechanosensitive ion channel TRPV4 normalizes tumor vasculature and improves cancer therapy.
Oncogene
January 2016
Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.
Tumor vessels are characterized by abnormal morphology and hyperpermeability that together cause inefficient delivery of chemotherapeutic agents. Although vascular endothelial growth factor has been established as a critical regulator of tumor angiogenesis, the role of mechanical signaling in the regulation of tumor vasculature or tumor endothelial cell (TEC) function is not known. Here we show that the mechanosensitive ion channel transient receptor potential vanilloid 4 (TRPV4) regulates tumor angiogenesis and tumor vessel maturation via modulation of TEC mechanosensitivity.
View Article and Find Full Text PDFSensitisation of TRPV4 by PAR2 is independent of intracellular calcium signalling and can be mediated by the biased agonist neutrophil elastase.
Pflugers Arch
April 2015
Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstr. 6, 91054, Erlangen, Germany.
Proteolytic activation of protease-activated receptor 2 (PAR2) may represent a major mechanism of regulating the transient receptor potential vanilloid 4 (TRPV4) non-selective cation channel in pathophysiological conditions associated with protease activation (e.g. during inflammation).
View Article and Find Full Text PDFBenzothiophene containing Rho kinase inhibitors: Efficacy in an animal model of glaucoma.
Bioorg Med Chem Lett
June 2010
Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA.
We identified a new benzothiophene containing Rho kinase inhibitor scaffold in an ultra high-throughput enzymatic activity screen. SAR studies, driven by a novel label-free cellular impedance assay, were used to derive 39, which substantially reduced intraocular pressure in a monkey model of glaucoma-associated ocular hypertension.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!