Navigation Links
New drug agent knocks out multiple enzymes in cancer pathway
Date:3/25/2009

A team of 24 researchers from the U.S., Europe, Taiwan and Japan and led by University of Illinois scientists has engineered a new anti-cancer agent that is about 200 times more active in killing tumor cells than similar drugs used in recent clinical trials.

The study appears this week in the Journal of the American Chemical Society.

The new agent belongs to a class of drugs called bisphosphonates. These compounds were originally developed to treat osteoporosis and other bone diseases, but were recently found to also have potent anti-cancer and immune boosting properties.

Drug developers have tried for years to design drugs to inhibit cell survival pathways in tumor cells, focusing on a protein called Ras since nearly a third of all human cancers involve a mutation in the Ras gene that causes cell signaling to go awry. These efforts have met with limited success.

Bisphosphonates act on other enzymes, called FPPS and GGPPS, which are upstream of Ras in the cell survival pathway. Inhibiting these enzymes appears to be a more effective strategy for killing cancer cells.

When used in combination with hormone therapy in a recent clinical trial, the bisphosphonate drug zoledronate significantly reduced the recurrence of breast cancer in premenopausal women with estrogen-receptor-positive breast cancer. Similar results were reported previously for hormone-refractory prostate cancer.

But zoledronate quickly binds to bone, reducing its efficacy in other tissues.

"We're trying to develop bisphosphonates that will be very active but won't bind to the bone, because if they bind to the bone they're not going to go to breast, lung or other tissues," said University of Illinois chemistry professor Eric Oldfield, who led the new study.

Oldfield's team also wanted to design a compound that would inhibit multiple enzymes in the tumor cell survival pathway, rather than just one, an approach analogous to the use of multi-kinase inhibitors in cancer therapy.

Andrew Wang, of Academia Sinica, Taipei, and Illinois chemist Rong Cao began by producing crystallographic structures of the target enzymes and drug candidates, allowing the researchers to identify those features that would enhance the drugs' ability to bind to the enzymes. Using this and other chemical data, Illinois chemistry department research scientist Yonghui Zhang engineered new bisphosphonate compounds that bound tightly to multiple enzyme targets, but not to bone.

One of the new compounds, called BPH-715, proved to be especially potent in cell culture and effectively inhibited tumor cell growth and invasiveness.

Tadahiko Kubo, of Hiroshima University, then found that BPH-715 also killed tumor cells in mice. And Socrates Papapoulos, of Leiden University, the Netherlands, showed that the compound had a very low chemical affinity for bone.

In humans, compounds like BPH-715 and zoledronate have an added benefit in fighting cancer: They spur the proliferation of immune cells called gamma delta T-cells, which aid in killing tumor cells.

"The new drugs are about 200 times more effective than the drugs used in recent clinical trials at killing tumor cells and in activating gamma delta T-cells to kill tumor cells," Oldfield said. "They also prevent tumor progression in mice much better than do existing bisphosphonate molecules."


'/>"/>

Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

Related biology news :

1. Structure of enzyme against chemical warfare agents determined
2. Chemopreventive agents in black raspberries identified
3. MIT nanotubes sniff out cancer agents in living cells
4. Exposure to Agent Orange linked to prostate cancer in Vietnam veterans
5. Certain anticancer agents could be harmful to patients with heart disease
6. UF researchers develop improved gene therapy agent
7. New insights into the diversity of Creutzfeldt-Jakob disease agents
8. Drug aimed at 2 bioterror agents blocks live viral infection, Weill Cornell team reports
9. Contrast agent trials in swine
10. Agent that triggers immune response in plants is uncovered
11. Primate behavior explained by computer agents
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New drug agent knocks out multiple enzymes in cancer pathway
(Date:12/16/2016)... DUBLIN , Dec 16, 2016 Research ... Access System Market - Global Forecast to 2021" report to ... ... projected to grow at a CAGR of 14.06% from 2016 to ... 2016, and is projected to reach 854.8 Million by 2021. The ...
(Date:12/15/2016)... and BADEN-BADEN, Germany , December 15, 2016 ... financial services provider, today announced an agreement with NuData Security, ... to join forces. The partnership will enable clients to focus ... compliance with local data protection regulation. ... In order to provide a ...
(Date:12/15/2016)... DUBLIN , Dec 15, 2016 ... Research and Markets has announced ... to their offering. The report forecasts the global military ... 2016-2020. The report has been prepared based on an ... market landscape and its growth prospects over the coming years. The report ...
Breaking Biology News(10 mins):
(Date:1/23/2017)... , Jan. 23, 2017  Alkahest Inc. ... treatments for neurodegenerative diseases and other age-related conditions, ... the company as Chief Medical Officer. In this ... clinical development activities at Alkahest and serve on ... most recently served as Executive Director at Dynavax, ...
(Date:1/23/2017)... ... January 23, 2017 , ... CallTower is proud to announce ... of the Year Award winner for 2017. , For three consecutive years, CallTower ... In 2016, CallTower was awarded with the hosted VoIP Excellence award and in 2015, ...
(Date:1/21/2017)... ... January 20, 2017 , ... Nipro Corporation (Osaka, Japan) and Transonic Systems Inc. ... will receive exclusive marketing and sales rights for all non-OEM Transonic products in Japan. ... in Japan, the new Nipro - Transonic JV is a natural next step to ...
(Date:1/21/2017)... 2017 Interpace Diagnostics Group, Inc. (NASDAQ: ... clinically useful molecular diagnostic tests and pathology services, ... securities purchase agreement with three  institutional investors to ... stock in a registered direct offering.  In a ... sell to the same investors warrants to purchase ...
Breaking Biology Technology: