Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

05 Mar 2017 - 09 Mar 2017
20 Mar 2017 - 23 Mar 2017
12 Apr 2017 - 14 Apr 2017

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

By BiotechDaily International staff writers
Posted on 26 Mar 2013
ADVERTISEMENT
SARTORIUS AG
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


Channels

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.