Biotech Values

[biomaven0]

>PDE-10

As far as I know there has only been one PDE-10 inhibitor in the clinic, and that only in a PET study of glucose metabolism:

http://clinicaltrials.gov/ct2/show/NCT01103726?term=pde-10&rank=1

But other big pharma do seem to be chasing this target:

Bioorg Med Chem Lett. 2012 Jan 1;22(1):235-9. Epub 2011 Nov 16.
Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia.
Yang SW, Smotryski J, McElroy WT, Tan Z, Ho G, Tulshian D, Greenlee WJ, Guzzi M, Zhang X, Mullins D, Xiao L, Hruza A, Chan TM, Rindgen D, Bleickardt C, Hodgson R.
Source
Department of Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States. [e-mail]
Abstract
A series of pyrazoloquinoline analogs have been synthesized and shown to bind to PDE10 with high affinity. From the SAR study and our lead optimization efforts, compounds 16 and 27 were found to possess potent oral antipsychotic activity in the MK-801 induced hyperactive rat model.

Here's some discussion of the theory behind this target - obviously this is a high-risk venture though:

CNS Drugs. 2008;22(12):983-93. doi: 10.2165/0023210-200822120-00002.
The role of phosphodiesterases in schizophrenia : therapeutic implications.
Siuciak JA.
Source
Neuroscience Department, Bristol-Myers Squibb Co., Wallingford, Connecticut 06492, USA. [e-mail]
Abstract
Recent studies have suggested that currently available antipsychotic medications, while useful in treating some aspects of schizophrenia, still possess considerable limitations. Improving the treatment of negative symptoms and cognitive dysfunction, and decreasing adverse effects remain significant challenges. Many new drug strategies have been proposed in recent years and increasing evidence suggests that members of the phosphodiesterase (PDE) gene family may play a role in the aetiology or treatment of schizophrenia. PDEs are key enzymes responsible for the degradation of the second messengers cAMP (3',5'-cyclic adenosine monophosphate) and cGMP (3',5'-cyclic guanosine monophosphate). Mammalian PDEs are composed of 21 genes and are categorized into 11 families based on sequence homology, enzymatic properties and sensitivity to pharmacological inhibitors. Representatives from most families have been identified in the brain by the presence of protein or RNA, and numerous studies suggest that PDEs play an important role in the regulation of intracellular signalling downstream of receptor activation in neurons. Insights into the multiple brain processes to which PDEs contribute are emerging from the phenotype of genetically engineered mice that lack activity of specific PDEs (knockout mice), as well as from in vitro and in vivo studies with PDE inhibitors.This article provides a brief overview of recent studies implicating PDE inhibition, focusing on PDE4 and PDE10, as targets for treating the positive, negative or cognitive symptoms associated with schizophrenia.