Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inhibitors of infamous Ras oncogene reported by Genentech researchers at ASCB annual meeting

05.12.2011
Making the 'undruggable' Ras oncogene 'druggable'

A drug discovery team at Genentech, Inc., has uncovered a chink in the molecular armor of Ras, the most commonly occurring oncogene, which is a gene that when mutated has the potential of causing cancer in humans.

The chink, binding pocket of "functional significance" on the Ras oncoprotein could provide the long-sought attack point for a therapeutic agent, making the "undruggable" Ras oncogene "druggable," the researchers reported at the American Society for Cell Biology's 51st Annual Meeting in Denver.

The first human oncogene to be identified, Ras is mutated in about 25% of all human tumors. For cancer patients, the presence of an activated Ras oncogene is a poor prognosis marker.

Ras has a molecular on-off switch, activated by the energy transfer molecule GTP. In the "on" position, the oncogene activates critical cell signaling pathways involving cell proliferation, cell migration and cell differentiation, all of which are in hyper-drive in tumors.

To develop a drug that would switch off Ras, scientists needed a binding site, an opening in the Ras oncoprotein to which the docking mechanism of a therapeutic molecule could attach.

At the ASCB meeting, Joachim Rudolph, Ph.D., Weiru Wang, Ph.D., and Guowei Fang, Ph.D., of Genentech, a member of the Roche Group, reported that they identified such a binding pocket by fragment-based lead discovery, a screening process that sorted through 3,300 small molecule compounds. Nuclear magnetic resonance (NMR) spectroscopy was used to pinpoint molecules with even a weak affinity for binding to Ras oncoproteins. The researchers identified 25 compounds, none of which knocked out the oncoprotein.

However, NMR spectroscopy revealed that the 25 compounds were binding to the same location on the Ras oncoprotein. The researchers determined that the binding pocket was not static but could be enlarged once the ligand from the small molecule engaged it, providing researchers an opening for engineering the next generation of compounds.

Fang said that even the weak ligands formed by these compounds interfered with the Ras oncoprotein by blocking an enzyme, abbreviated SOS, that is required for activating the oncoprotein.

"The small molecules identified here represent the first generation of Ras inhibitors that directly prevent Ras activation," Fang said.

CONTACT:

Guowei Fang, Ph.D. Genentech, Inc. Fang.guowei@gene.com 650-228-8497

Robin Snyder, Ph.D. Director, External Communications Genentech Corporate Relations 650.467.7152 snyder.robin@gene.com

John Fleischman American Society for Cell Biology jfleischman@ascb.org 513-929-4635 513-706-0212 (cell)

Cathy Yarbrough American Society for Cell Biology sciencematter@yahoo.com 858-243-1814

AUTHOR PRESENTS:

Sunday, Dec. 4, 2011 5:35 to 5:55 p.m. Minisymposium: Chemical Biology: Probes and Therapeutics Presentation 24

John Fleischman | EurekAlert!
Further information:
http://www.ascb.org

Further reports about: ASCB Genentech Inhibitors NMR cell death signaling pathway synthetic biology

More articles from Life Sciences:

nachricht Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>