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: Investigators insert large DNA sequence into mammalian cells

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.

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

Unlocking lignin for sustainable biofuel

35 minutes ago

Turning trees, grass, and other biomass into fuel for automobiles and airplanes is a costly and complex process. Biofuel researchers are working to change that, envisioning a future where cellulosic ethanol, ...

Scientists develop free, online genetic research tool

1 hour ago

Technology rapidly is advancing the study of genetics and the search for causes of major diseases. Analysis of genomic sequences that once took days or months now can be performed in a matter of hours. Yet, ...

Why do strawberries taste so good?

10 hours ago

Each year, spectators at the Wimbledon tennis tournament get through a whopping 30 tons of strawberries in the course of a summer fortnight. It is no wonder that the association between Wimbledon and strawberries ...

Investigators insert large DNA sequence into mammalian cells

Jul 06, 2015

For the first time, researchers have used a simplified technique derived from a defense mechanism evolved by bacteria and other single-celled organisms to successfully insert a large DNA sequence into a predetermined genomic ...

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.