deCODE Files IND for DG071, a Novel PDE4 Modulator Being Developed for Alzheimer's and Other Cognitive... (remaining neurons to store and retrieve ...)

deCODE Files IND for DG071, a Novel PDE4 Modulator Being Developed for Alzheimer's and Other Cognitive Disorders

Date:10/3/2008

remaining neurons to store and retrieve memories more efficiently. DG071 could be useful in the treatment not only of Alzheimer's disease, but might also have benefit in Huntington's disease, schizophrenia, anxiety, ADHD and depression," said Dr. Kari Stefansson, CEO of deCODE.

DG071 is a novel, potent and selective PDE4D modulator discovered by deCODE's chemistry group. First and second generation PDE4 inhibitors such as rolipram, cilomilast, and roflumilast caused significant side effects, including nausea and vomiting, at the therapeutic doses in human clinical trials. Such side effects severely limit the utility of these earlier compounds. Data generated at deCODE suggest that the observed side effects were closely correlated with the binding of these molecules in the PDE4 enzymatic active site competitively with cAMP. As cAMP is of critical importance to neuronal signalling, the goal of deCODE's program has been to discover compounds that would modulate PDE4 activity via an allosteric mechanism to improve safety and tolerability.

Towards this goal, the deCODE biostructures team solved multiple novel co-crystal structures of PDE4D & PDE4B containing regulatory domains with bound ligands. Those structures allowed the deCODE chemistry team to identify a novel binding site for allosteric modulators in the PDE4 regulatory domain. Binding of an allosteric modulator at that site is non-competitive with cAMP. DG071 has been shown in animal models to improve cognitive function with benefit similar to that of cholinesterase inhibitors such as donepezil that currently are a mainstay of therapy for memory loss in early Alzheimer's disease, yet also benefiting long term memory function in animal tests where the cholinesterase inhibitors are ineffective.

deCODE has developed a broad proprietary platform for PDE4 modulators that the company is applying to discover compounds with potential utility for the treatment of over-active bladder, inflammatory and
'/>"/>

1

GOOD

Page: 1 2 3 4 5
Related medicine technology :

1. deCODE and Radboud University Discover Common Variants in the Human Genome Conferring Risk of Bladder Cancer
2. deCODE and SGENE Consortium Discover Deletions in the Human Genome Linked to Risk of Schizophrenia
3. Marketing of Diagnostics and deCODEme(TM), Recent Progress in Drug Development to be Highlighted at deCODE R&D Event
4. deCODE Discovers Novel Genetic Links Between Pigmentation Traits and Risk of Skin Cancer
5. deCODE Obesity Study Sheds Light on How Genetics Affects Risk and Onset of Common Diseases
6. deCODE Launches a DNA-Based Test for Assessing Risk of Prostate Cancer on the Back of the Discovery of New Prostate Cancer Genes
7. deCODE Launches deCODE MI(TM) -- A Test for a Major Genetic Risk Factor for Early-onset Heart Attack
8. deCODE Launches Phase II Clinical Testing of DG051 for the Prevention of Heart Attack
9. ASX/NASDAQ Media Release: Pharmaxis Files First Marketing Application for Bronchitol in Australia
10. Sound Pharmaceuticals Files Second IND with the FDA for the Prevention of Chemotherapy Induced Hearing Loss in Advanced Stage Cancer
11. FDA Files Application To Convert ONTAK(R) (Denileukin Diftitox) to Full Approval for Use in Cutaneous T-Cell Lymphoma (CTCL)

Post Your Comments:

deCODE Files IND for DG071, a Novel PDE4 Modulator Being Developed for Alzheimer's and Other Cognitive...(remaining neurons to store and retrieve ...),Health