Navigation Links
New Candidate Drug Stops Cancer Cells, Regenerates Nerve Cells

CINCINNATI, June 21, 2012 /PRNewswire-USNewswire/ -- Scientists have developed a small-molecule-inhibiting drug that in early laboratory cell tests stopped breast cancer cells from spreading and also promoted the growth of early nerve cells called neurites.


Researchers from Cincinnati Children's Hospital Medical Center report their findings online June 21 in Chemistry & Biology. The scientists named their lead drug candidate "Rhosin" and hope future testing shows it to be promising for the treatment of various cancers or nervous system damage.

The inhibitor overcomes a number of previous scientific challenges by precisely targeting a single component of a cell signaling protein complex called Rho GTPases. This complex regulates cell movement and growth throughout the body. Miscues in Rho GTPase processes are also widely implicated in human diseases, including various cancers and neurologic disorders.  

"Although still years from clinical development, in principle Rhosin could be useful in therapy for many kinds of cancer or possibly neuron and spinal cord regeneration," said Yi Zheng, PhD, lead investigator and director of Experimental Hematology and Cancer Biology at Cincinnati Children's. "We've performed in silica (computerized) rational drug design, pharmacological characterization and cell tests in the laboratory, and we are now starting to work with mouse models."

Because the role of Rho GTPases in cellular processes and cancer formation is well established, researchers have spent years trying to identify safe and effective therapeutic targets for specific parts of the protein complex. In particular, scientists have focused on the center protein in the complex called RhoA, which is essential for the signaling function of the complex. In breast cancer for example, increased RhoA activity makes the cancer cells more invasive and causes them to spread, while a deficiency of RhoA suppresses cancer growth and progression.

Despite this knowledge, past efforts to develop an effective small-molecule inhibitor for RhoA have failed, explained Zheng, who has studied Rho GTPases for over two decades. Most roadblocks stem from a lack of specificity in how researchers have been able to target RhoA, a resulting lack of efficiency in affecting molecular processes, problems with toxicity, and the inability to find a workable drug design.

For the current study, Zheng and his colleagues started with the extensive body of research from Cincinnati Children's and other institutions describing the processes and functions of Rho GTPases. They then used high-throughput computerized molecular screening and computerized drug design to reveal a druggable target site. This also provided a preliminary virtual simulation on the potential effectiveness of candidate drugs.

A key challenge to binding a small-molecule inhibitor to RhoA is the protein's globular structure and lack of surface pocket areas suitable for easy binding, Zheng said. The unique chemical structure of the lead compound identified by researchers, Rhosin, allows it to effectively bind to two shallow surface grooves on RhoA. This enables the candidate drug to take root and begin affecting cells. The two-legged configuration of Rosin also describes a useful drug design strategy for more effectively targeting difficult molecular sites like RhoA.

The researchers also wanted to make sure Rhosin effectively blocked what are known as guanine nucleotide exchange factors (GEFs). Guanine nucleotide is a critical energy source and signaling component of cells. Activation of GEFs is required to set off the regulatory signaling of GTPases (GTP stands for guanosine triphosphate).

After conducting a series of laboratory cell tests to verify the targeting and binding capabilities of Rhosin to RhoA, the researchers then tested the candidate drug's impact on cultured breast cancer cells and nerve cells.

In tests on a human breast cancer cells, Rhosin inhibited cell growth and the formation of mammary spheres in a dose dependent manner, acting specifically on RhoA molecular targets without disrupting other critical cellular processes. Rhosin does not affect non-cancerous breast cells. This, along with other tests the scientists performed, indicated Rhosin's effectiveness in targeting RhoA-mediated breast cancer proliferation, according to the researchers.

Researchers also treated an extensively tested line of neuronal cells with Rhosin, along with nerve growth factor, a protein that is important to the growth and survival of neurons. Rhosin worked with nerve growth factor in a dose-dependent way to promote the proliferation of branching neurites from the neuronal cells. Neurites are young or early stage extensions from neurons required for neuronal communications.

Funding for the study came from National Institutes of Health.

Also collaborating on the study were NanoTemper Technologies in Munich, Germany and the Drug Discovery Center at the University of Cincinnati.

About Cincinnati Children's
Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2012 Best Children's Hospitals ranking. It is ranked #1 for neonatology and in the top 10 for all pediatric specialties. Cincinnati Children's is one of the top two recipients of pediatric research grants from the National Institutes of Health. It is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at

SOURCE Cincinnati Children's Hospital Medical Center
Copyright©2012 PR Newswire.
All rights reserved

Related medicine technology :

1. Polaris Group Lead Therapeutic Candidate ADI-PEG 20 Demonstrates Potential Anticancer Activity in Various Metastatic Sarcomas and Bladder Cancers That Are Deficient in Key Metabolic Protein, and Enhanced Effects with Combination Therapy in Melanoma
2. Flexions Lead Osteoarthritis Drug Candidate Demonstrates Significant, Prolonged Improvement in Pain and Function in Phase 2 Trial
3. Marshall Edwards Announces First Cohort Of Patients Dosed In Phase I Clinical Trial Of Oncology Drug Candidate ME-344
4. Lilly Diabetes Presents Phase II Blood Pressure and Heart Rate Data on Investigational GLP-1 Analog Candidate, Dulaglutide, in Patients with Type 2 Diabetes at the 27th American Society of Hypertension Scientific Meeting
5. Xiangxue Pharmaceuticals to Acquire Rights for a Promising Drug Candidate from Kinex Pharmaceuticals for the Greater China Territory
6. Rigel Advances Asthma Programs: Two Inhaled Drug Candidates Take Aim at Acute and Chronic Lung Disease
7. Alder BioPharmaceuticals Inc. Initiates Phase 1 Clinical Study of Antibody Therapeutic Candidate for Treatment of Migraine, ALD403
8. Breakthrough Prostate Cancer Diagnostics
9. Austrian Medical Center Upgrades Cancer Treatment System, Improves Patient Care with Elektas Agility Beam-shaping Device
10. European Hematology Association, American Society of Hematology, and the European Cancer Patient Coalition Issue an International Call to Action to Alleviate Drug Shortages
11. Generex Announces Interviews Featuring the Antigen Express AE37 Breast Cancer Vaccine at ASCO 2012
Post Your Comments:
(Date:11/26/2015)... -- Research and Markets ( ) has ... Horizons and Growth Strategies in the Italian Therapeutic ... Forecasts, Competitive Intelligence, Emerging Opportunities" report to ... --> This new 247-page report provides ... monitoring market, including emerging tests, technologies, instrumentation, sales ...
(Date:11/25/2015)... , Nov. 25, 2015 ... the addition of the "Global Brain ... their offering. --> ) ... "Global Brain Monitoring Devices Market 2015-2019" ... Research and Markets ( ) has ...
(Date:11/25/2015)...  The American Academy of Pediatrics (AAP), American ... March of Dimes cheered today,s signature into law ... of 2015 (S.799), which takes much-needed strides ... to drugs, such as opioids, and to improve ... organizations have worked together leading advocacy efforts for ...
Breaking Medicine Technology:
(Date:11/29/2015)... Jose, CA (PRWEB) , ... November 29, 2015 , ... ... Area, is proud to announce their December, 2015, featured apartment community: Epic. In showcasing ... for corporate housing in the tight Bay Area rental market to efficiently find housing ...
(Date:11/28/2015)... ... ... November 30th at 6:00 a.m. EST until 11:59 p.m. EST, customers will ... to 20% off orders $80 or more to free gifts with purchases, there will be ... a competitive e-commerce website for skin care and cosmetic needs, customers will save on already ...
(Date:11/27/2015)... ... , ... According to an article published November 6th by The ... of British Columbia suggested that laws requiring bicyclists to wear helmets may not actually ... the reason for the controversial conclusion is that, while helmets have certainly prevented a ...
(Date:11/27/2015)... ... November 27, 2015 , ... An inventor, from ... dispense prescription medications at home, so he invented the patent-pending ELECTRONIC M.D. , ... prescription medications. In doing so, it could help to prevent potential overdose situations. ...
(Date:11/27/2015)... ... ... ProSidebar: Fashion is a set of 30 kinetic edge graphics ... editors can easily add an informative sidebar to any FCPX production. Create lists, ... self-animating drop zones, lines, bars, and text with the ease of FCPX's drag and ...
Breaking Medicine News(10 mins):