ArQule moves forward with their cell cycle modulator...Wyeth develops selective GABA(A) alpha2/alpha3 subtype agonists as candidate anxiolytics

Todays Headlines from across the DailyUpdates network (20th June, 2006): We highlight research from Merck who are developing a novel approach to anxiety and news from ArQule on their oncology candidate - to view today's bulletin in its entirety click here or read on for further information on these two publications

• Breaking News (from DailyUpdates-Oncology): ArQule moves forward with their cell cycle modulator The cell cycle and check-points within the cycle represent a major focus of drug development companies attempting to introduce new cancer therapeutics. One group of molecular targets under investigation is the aurora kinase family (see LeadDiscovery's recent feature Aurora Kinase inhibitors - The dawn of a new approach to cancer). In addition, over the past few weeks we have highlighted work by ArQule who are targeting E2F1 in an attempt to regulate cell cycle checkpoints. At the begining of April (2006) we highlighted a company release reporting Phase 1 monotherapy data demonstrating efficacy in cancer patients with advanced solid tumors who had failed prior treatments with chemotherapy. Today we headline with a further release from the company announcing the enrollment and successful dosing of the first patient in a Phase 2 clinical trial of ARQ 501 in combination with gemcitabine to treat pancreatic cancer. Pancreatic cancer is the fifth leading cancer-related cause of death and is thus a major health issue in the developed world. Its aggressive nature and resistance to conventional therapy results in an exceedingly poor prognosis. For the foreseeable future, gemcitabine will remain the gold-standard treatment for pancreatic cancer and retain its status as market leader. Despite an active late-phase pipeline, no agent is seriously threatening gemcitabine's position (see our feature Pancreatic Cancer - Gold Standard Gemcitabine Waiting to be Challenged). Commercial potential will be increased if benefit is demonstrated in combination with gemcitabine and it is hoped that the trial announced today will move some way towards this goal.[Source: ArQule Release]

Featured Journal Article (from DailyUpdates-Psychiatric Disorders): Wyeth develops selective GABA(A) alpha2/alpha3 subtype agonists as candidate anxiolytics: The global anxiety disorders market is set to decline from $4.5 billion in 2006 to $2.6 billion by 2015 (Anxiety Disorders - A decade of declining revenues). This will be primarily due to the launch of numerous generic anxiety drugs from 2006 onwards, which will offset the revenue growth derived from existing drugs seeking additional anxiety indications, and the launch of several novel anxiety drugs. Novel anxiety drugs expected to be launched after 2006 include Predix's 5-HT1A agonist PRX-00023. In addition to serotonin receptor ligands, benzodiazepine binding-site agonists, exemplified by diazepam, have proven anxiolytic efficacy. This class is however disadvantaged by adverse effects including sedation, physical dependence and a potential for abuse. It is now known that the alpha2- and/or alpha3 subunits of the GABA(A) receptor mediates the anxiolytic activity of benzodiazepines whereas the alpha1 subtype is involved in sedation, prompting the development of selective alpha2- and/or alpha3-receptor agonists. Today’s featured journal article reports on studies conducted by Merck researchers culminating in the development of a series of GABA(A) alpha2/alpha3 subtype selective agonists. These anxiolytic agents with reduced sedative/ataxic potential display good CNS penetration and oral bioavailability thus representing clinical candidates [Source: J Med Chem. 2006 Apr 20;49(8):2600-10]