Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

Virtual Screening Identifies New Low Molecular Weight Anticancer Drug Candidates

By BiotechDaily International staff writers
Posted on 21 Feb 2013
Computer modeling and high throughput molecular screening were used to identify low molecular weight compounds capable of blocking the activity of procancerous signaling molecules called G-protein mediated Rho guanine nucleotide exchange factors (GEFs).

GEFs have been implicated in several human diseases including cancer, but finding suitable drugs to block their activity has proven difficult due to a lack of distinctive formational features in the three-dimensional structure of these molecules. Investigators at Cincinnati Children's Hospital Medical Center (OH, USA) have approached this problem from a new direction.

They reported in the February 4, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that they had virtually screened chemicals that fit into a surface groove of the DH-PH domain of LARG (leukemia-associated Rho guanine nucleotide exchange factor), a G-protein-regulated Rho GEF involved in RhoA activation, and had followed up the virtual tests with validations in biochemical assays. This methodology allowed them to identify a class of chemical inhibitors represented by Y16 that was active in specifically inhibiting LARG binding to RhoA.

RhoA (Ras homolog gene family, member A) is a small GTPase protein known to regulate the actin cytoskeleton in the formation of stress fibers. This protein is essential for the signaling function of the Rho GTPase complex. Previous studies have shown that in breast cancer increased RhoA activity stimulated cancer cell invasiveness and spreading, while RhoA deficiency suppressed cancer growth and progression. In addition to its role in breast cancer, imbalance in Rho GTPase activity has been implicated in other human diseases, including various cancers and neurological disorders.

The suppressive effect of Y16 was significantly amplified by using the compound together with Rhosin/G04, a drug previously shown to target RhoA. The combination of Y16 and Rhosin/G04 did not interfere with other cellular signaling functions.

"We are using the findings from this study to refine our compounds and test them on mouse models of acute myeloid leukemia and certain metastatic tumors—especially breast cancer, where the target pathway of this lead inhibitor is hyperactive," said senior author Dr. Yi Zheng, professor of pediatrics at Cincinnati Children's Hospital Medical Center.

Related Links:
Cincinnati Children's Hospital Medical Center


Channels

Genomics/Proteomics

view channel
Image: Transmission electron micrograph of norovirus particles in feces (Photo courtesy of Wikimedia Commons).

Norovirus Interacts with Gut Bacteria to Establish a Persistent Infection That Can Be Blocked by Interferon Lambda

A team of molecular microbiologists and virologists has found that norovirus requires an intimate interaction with certain gut bacteria to establish a persistent infection, and that the infective process... Read more

Drug Discovery

view channel

Curcumin Used to Treat Alzheimer’s Disease

Curcumin, a natural substance found in the spice turmeric, has been used by many Asian cultures for centuries. Now, new research suggests that a close chemical analog of curcumin has properties that may make it useful as a treatment for Alzheimer’s disease. “Curcumin has demonstrated ability to enter the brain, bind... Read more

Biochemistry

view channel
Image: Induced pluripotent stem (iPS) cells, which act very much like embryonic stem cells, are shown growing into heart cells (blue) and nerve cells (green) (Photo courtesy of Gladstone Institutes/Chris Goodfellow).

Methodology Devised to Improve Stem Cell Reprogramming

In a study that provides scientists with a critical new determination of stem cell development and its role in disease, researchers have established a first-of-its-kind approach that outlines the stages... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.