Emerald BioStructures announces discovery of small molecule modulators of PDE4

Dec 27, 2009

Emerald BioStructures (formerly deCODE biostructures) announced a publication in the December 27, 2009 advance online issue of Nature Biotechnology, detailing the application of structure-based drug design (SBDD) to engineer new allosteric small molecule modulators of the enzyme phosphodiesterase-4 (PDE4), with reduced side effects. According to the paper, the researchers established the structural basis of PDE4 regulation through crystal structures of the PDE4 regulatory domain in contact with small molecules.

"This paper demonstrates Emerald's ability to address key challenges in through our world-class X-ray crystallography and structure-based design capabilities," said Lance Stewart, Chief Executive Officer of Emerald BioStructures. "Our approach allows us to deliver valuable, 'game-changing' information in active areas of drug discovery and development, including intracellular protein-protein interactions, as shown in this case. I believe this expertise establishes Emerald BioStructures as a valuable partner to companies that need help solving their important problems in drug discovery, such as reaching historically undruggable targets."

PDE4 is an important therapeutic target, due to its involvement in an array of inflammatory diseases including asthma, psoriasis and COPD, and central nervous system disorders including schizophrenia, Alzheimer's disease, and other cognitive impairments. However, previously developed PDE4 inhibitors have been associated with side effects that have severely limited their potential as potential therapies, and no PDE4 inhibitor has been FDA-approved.

Dr. Alex Burgin, Chief Operating Officer of the Company and one of the corresponding authors on the paper, said, "Establishing novel PDE4 regulatory domain crystal structures enabled our research team to develop small molecules that interact with those regulatory domains and only partially inhibit enzyme activity. As a result, these newly reported modulators do not have the side effects of traditional inhibitors, but have maintained therapeutic activity and efficacy in preclinical models of cognition. This is a strong demonstration of Emerald's ability to use its structural-based insights to rationally design enhanced and selective drug candidates."

Explore further: Scientists tap trees' evolutionary databanks to discover environment adaptation strategies

More information: "Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety," was authored by Alex B. Burgin, Olafur T. Magnusson, Jasbir Singh, Pam Witte, Bart L. Staker, Jon M. Bjornsson, Margret Thorsteinsdottir, Sigrun Hrafnsdottir, Timothy Hagen, Alex S. Kiselyov, Lance J. Stewart and Mark E. Gurney.

Source MacDougall Biomedical Communications

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Researchers identify new drug target for Kaposi's sarcoma

Jul 30, 2009

UCSF researchers have identified a new potential drug target for the herpes virus that causes Kaposi's sarcoma, re-opening the possibility of using the class of drugs called protease inhibitors against the full herpes family ...

New computational technique can predict drug side effects

Dec 11, 2007

Early identification of adverse effects of drugs before they are tested in humans is crucial in developing new therapeutics, as unexpected effects account for a third of all drug failures during the development process.

Recommended for you

Keep dogs and cats safe during winter

9 hours ago

(HealthDay)—Winter can be tough on dogs and cats, but there are a number of safe and effective ways you can help them get through the cold season, an expert says.

Scientists target mess from Christmas tree needles

Dec 26, 2014

The presents are unwrapped. The children's shrieks of delight are just a memory. Now it's time for another Yuletide tradition: cleaning up the needles that are falling off your Christmas tree.

Top Japan lab dismisses ground-breaking stem cell study

Dec 26, 2014

Japan's top research institute on Friday hammered the final nail in the coffin of what was once billed as a ground-breaking stem cell study, dismissing it as flawed and saying the work could have been fabricated.

Research sheds light on what causes cells to divide

Dec 24, 2014

When a rapidly-growing cell divides into two smaller cells, what triggers the split? Is it the size the growing cell eventually reaches? Or is the real trigger the time period over which the cell keeps growing ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.