Tag: PDE10

Company News: biocrea and Pfizer Jointly Presented Details on Novel PDE10 Inhibitors at the 241st ACS National Meeting & Exposition

– Novel treatment opportunities for CNS diseases –

biocrea, a biopharmaceutical company focusing on novel treatments for disorders of the central nervous system (CNS), today reported details on the design and synthesis of novel, brain-penetrating phosphodiesterase-10 (PDE10) inhibitors developed in collaboration with Pfizer Inc. (NYSE: PFE). The data were featured in joint presentations[1] with Pfizer at the recent 241st ACS National Meeting & Exposition, an event organized by the American Chemical Society (ACS).

The data demonstrated that the scientists at Pfizer and biocrea were able to eliminate undesired activity on adenosine receptors and to considerably improve the compounds´ physicochemical properties and potency. The team had started with initial high-throughput hits characterized by low potency and selectivity. Further lead optimization led to a number of compounds with very robust activity in a range of preclinical models of anti-psychotic efficacy. Moreover, these PDE10 inhibitors produced low levels of catalepsy, suggesting a minimal risk for the induction of side-effects involving the extrapyramidal system (EPS), the most common adverse reaction observed with anti-psychotic drugs.

Phosphodiesterases (PDEs) have been identified as key regulators of intracellular cyclic nucleotide levels in the brain. Mechanistically, PDE10 inhibition has two major benefits, mimicking, (1) the effects of antagonists of the dopamine-2 receptor, the current standard treatment for psychosis, and (2) the effects of agonists of dopamine-1 receptors, which may decrease the side-effect liabilities while contributing to a pro-cognitive profile.

 

[1] Malamas M et al., 241st ACS National Meeting & Exposition Abstract 65 – Imidazo[1,5-a]quinoxalines as selective PDE10A inhibitors for the treatment of schizophrenia, http://redir.ec/Qr3C; Malamas, M. et al., 241st ACS National Meeting & Exposition Abstract 66 – Benzo[e]imidazo[5,1-c][1,2,4]triazines as selective PDE10A inhibitors for the treatment of schizophrenia, http://redir.ec/pl1Q


Company News: biocrea Announces Novel Treatment Opportunities for CNS Diseases

– Company has filed US patent on novel, brain-penetrating PDE2 and PDE10 inhibitors –

CNS company biocrea today announced it has filed a patent application covering its brain-penetrating inhibitors of phosphodiesterases. These compounds constitute a new generation of promising drug candidates to address several CNS disorders that are currently lacking effective treatment options. biocrea has submitted a patent application to the U.S. Patent Office (USPTO) covering compounds and uses of its proprietary PDE2 and PDE10 inhibitors.

While the inhibitors of PDE10 show excellent potential for the treatment of schizophrenia, Huntington’s disease and Tourette’s syndrome, the PDE2 inhibitors cover a whole spectrum of new biological activities and treatment opportunities. Moreover, biocrea’s brain-penetrating PDE2 inhibitors show promise for the treatment of drug-induced movement disorders.

biocrea’s patent application also comprises dual inhibitors of PDE2 and PDE10 as the combination of both modes of action in one molecule results in synergistic biological effects.

So far, validating the benefit of brain PDE inhibitors in CNS diseases has been difficult because access to brain PDEs is limited by the so-called “blood brain barrier” (BBB). The team of biocrea has overcome these limitations and developed brain-penetrating, highly specific PDE inhibitors that constitute a new generation of promising drug candidates for the treatment of CNS disorders. The most advanced compound of biocrea’s novel family of PDE inhibitors, a brain-penetrating, selective PDE2 inhibitor, has been selected to enter pre-clinical development.

Company News: biocrea acquires CNS pipeline and PDE inhibitor platform from Biotie

In a management-buyout, biocrea GmbH is taking over  the CNS pipeline and phosphodiesterase enzyme (PDE) inhibitor platform from Finnish Biotie Therapies Corp.

The company currently has a pipeline of three PDE inhibitors at research and preclinical stages, which will be advanced into clinical development by 2012. The compounds have already demonstrated efficacy in preclinical animal models for schizophrenia, memory impairment, depression and anxiety.

biocrea is based in Radebeul near Dresden, Germany, and will be led by Dr. Tom Kronbach, former CSO of Biotie.

More details can be found soon at biocrea’s website.