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

First-in-Class GTPase Inhibitor to Have Applications in Drug Discovery and Fundamental Research

By BiotechDaily International staff writers
Posted on 26 Mar 2013
A recent paper described the activity of a low molecular weight compound able to selectively inhibit the enzyme Cdc42 in biochemical and cellular assays that are expected to have applications in drug discovery and fundamental research.

Human Cdc42 is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis, and cell cycle progression. Overactive Cdc42 has been implicated in the pathology of cancers, immune diseases, and neuronal disorders. While Cdc42 inhibitors would be useful in probing molecular pathways and could have therapeutic potential, previous attempts to develop them have been unsuccessful, as the inhibitors have lacked selectivity and trended towards toxicity.

In the current study investigators at the University of New Mexico (Albuquerque, USA) succeeding in isolating a low molecular weight inhibitor of Cdc42 by high-throughput screening of hundreds of compounds.

They reported in the February 4, 2013, online edition of the Journal of Biological Chemistry that the compound, CID2950007, demonstrated excellent selectivity with no inhibition towards Rho and Rac from the same GTPase family. Biochemical characterization showed that the compound acted as a noncompetitive allosteric inhibitor. When tested in cellular assays, it inhibited Cdc42-related filopodia formation and cell migration.

CID2950007 was also used to clarify the involvement of Cdc42 in the internalization of Sin Nombre virus and the signaling pathway of integrin VLA-4.

“It is an important target in many diseases,” said senior author Dr. Angela Wandinger-Ness professor of pathology at the University of New Mexico. “Cancer is just one. But there were no compounds that target this GTPase. “There is a lot of enthusiasm for a compound like this—because there were not any. This is a first-in-class.”

Related Links:
University of New Mexico


WATERS CORPORATION

Channels

Genomics/Proteomics

view channel
Image: Mosquitoes are known to infect people and animals with West Nile virus. Studying West Nile virus infection in mice, researchers have shown that the antiviral compound interferon-lambda tightens the blood-brain barrier, making it harder for the virus to invade the brain (Photo courtesy of the CDC – [US] Centers for Disease Control and Prevention).

Interferon-Lambda Prevents West Nile Virus from Crossing the Blood-brain Barrier

The cytokine interferon-lambda prevents West Nile virus from infecting brain cells by reducing transport of large molecules across the blood-brain barrier. Although interferon-lambda [also known as... Read more

Lab Technologies

view channel
Image: The gene assembly robot, the GeneTheatre (Photo courtesy of Analytik Jena AG).

Genomic Research Laboratories Await New Compact Liquid Handling System

A small footprint benchtop liquid handler that automates multiple gene assembly tasks and associated procedures such as PCR setup is now available for use by biotech and genomic research laboratories.... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 

Events

27 May 2015 - 28 May 2015
02 Jun 2015 - 03 Jun 2015
15 Jun 2015 - 18 Jun 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.