-- Peer-Reviewed Data Demonstrates Usefulness and Robustness of In Silico
Technology and Validates Predix Discovery Engine --
WOBURN, Mass., and RAMAT-GAN, Israel, Aug. 18 /PRNewswire/ -- Predix
Pharmaceuticals Inc., a drug discovery and development company, announced
today that peer-reviewed data illustrating the company's repeated success in
using computerized 3D models of GPCR drug targets for blind in silico
screening was published in the August 3rd (Vol. 101, No. 31) issue of the
Proceedings of the National Academy of Sciences (PNAS). Additional data are
presented in the October 1, 2004, issue of the journal Proteins. These
publications present some of the most promising examples of the successful
utilization of in silico models for GPCR-targeted drug discovery. The
article, "G Protein-Coupled Receptors: In Silico Drug Discovery in 3D," shows
that the Company's proprietary PREDICT(TM) methodology achieved identification
of high-quality hits, including promising lead compounds directly out of the
in silico screening for multiple drug discovery programs - all utilizing
Predix's computer generated GPCR structures. By integrating this
computational technology with standard medicinal chemistry, Predix has created
several lead programs and has recently completed Phase I human studies with
their most advanced compound.
"We are extremely pleased with the outcome of our research using the
PREDICT(TM) 3D technology. The data presented demonstrate that the hits we
identified in silico -- and verified in standard biological assays -- serve as
high quality lead compounds for drug discovery," said Oren Becker, PhD, co-
founder and Chief Scientific Officer at Predix. "Using our extensive set of
proprietary GPCR and other protein structures, Predix was able to optimize a
selective 5-HT1A agonist in six months with only 31 compounds synthesized.
This work paves the way to a broader application of 3D models in GPCR drug
discovery and Predix Pharmaceuticals is leading the way in this important
field of research."
In this study reported in PNAS, the Company applied its PREDICT(TM)
technology to model the 3D structure of five different GPCR drug targets in
silico and then screened its virtual library of two million compounds against
these 3D models. Using proprietary docking and scoring algorithms, Predix
then selected the 100 top ranked compounds for each target. These compounds
were tested in standard assays, which demonstrated that 15% to 25% of the
compounds show potent binding to their respective targets. Many of these hits
exhibited a range of attractive drug properties qualifying them as lead
compounds for these specific drug discovery programs.
The Predix hit-to-lead and lead-optimization processes (structure-activity
determinations) utilize the 3D structure of the protein together with
proprietary algorithms which computationally prioritize hits and leads. Using
these algorithms, about 10% of molecules recommended in each lead optimization
cycle are actually synthesized by medicinal chemists. Thus, the speed and
accuracy of the company's drug discovery platform yields dramatic reductions
in cycle times, at least as efficiently as programs where the 3D structure of
the target protein is known. Predix has achieved its goals of moving from
initiation of a new project GPCR sequence up to submission of an
Investigational New Drug filing for entry into the clinic within 24 months for
its first program, and is expects to repeat this for two additional programs
within the next year.
About G-Protein-Coupled Receptors (GPCRs)
G-protein-coupled receptors are a pharmacologically important protein
family with over 800 genes identified to date. These proteins are responsible
for communications between the cell and its environment. Pathways involving
these receptors are the targets of 50% of all recently launched drugs
including those for the treatment of hypertension, cardiac dysfunction,
depression, anxiety and pain. Like other membrane-embedded proteins, GPCRs
have characteristics that make their native 3D structure extremely difficult
to determine experimentally. This difficulty motivates the search for
computational methods that can predict their structure with high reliability.
About PREDICT(TM)
PREDICT(TM) is a proprietary three-dimensional GPCR modeling technology
that combines the properties of a protein sequence with those of its membrane
environment without relying on x-ray crystallographic or other structural
methodologies. The PREDICT(TM) algorithm searches through the receptors'
conformation space for the most stable 3D structure of the TM domain of the
protein. To ensure the final model represents the most stable conformation,
the method simultaneously optimizes several thousand alternative conformations
of the receptor. Predix Pharmaceuticals Inc. has an exclusive worldwide
license to this technology.
About Predix
Predix is a drug development company integrating computational and
medicinal chemistry to rapidly and efficiently create new drugs targeted to
GPCRs and ion channels (IC). Leveraging its proprietary technology, Predix
has created a diverse clinical and pre-clinical stage drug development
pipeline focused in the GPCR and ion channel areas. The Company's current
pipeline includes one program which has completed Phase I clinical trials, two
programs in preclinical stage and four additional programs in lead discovery
and early lead optimization. Predix expects to retain a minority of its
clinical programs in house through Phase 2 and Phase 3 clinical trials, while
generating early upfront and milestone revenues, as well as royalties from
partnering some of its novel compounds following Phase I safety studies.
Predix was incorporated in December, 2000, and initiated its medicinal
chemistry and development activities, with its headquarters, in Woburn,
Massachusetts, in September, 2002. The Company was founded in Ramat Gan,
Israel, and maintains its computational chemistry division there.
Contact:
Christine Hayden
(781) 376-0821 Ext. 1010
http://www.predixpharm.com
SOURCE Predix Pharmaceuticals Inc.
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Related links:
http://www.predixpharm.com
CONTACT:
Christine Hayden of Predix Pharmaceuticals
Inc., +1-781-376-0821 Ext. 1010
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