This consists of 10 up regulated and 14 down regulated genes, which www.selleckchem.com/products/Cisplatin.html can be thought of as a binary signature for neuropathology, where 1 is assigned to up regulated genes and 1 to down regu lated genes, see Table 5. The CMAP drugs with the highest anti correlation with this signature are shown in Table 6. Remarkably, there are at least 9 neuroprotective agents in the top 22 hits. In particular, Galantamine, a plant alkaloid, is currently prescribed for early stage AD, it was originally studied for its acetylcholinester ase inhibitory activity, but it may also act on other tar gets. The flavones chrysin, apigenin and luteolin have been reported to have neu roprotective activity. As have the two kinase inhibitors H 7 and GW 8510. The b carboline plant alkaloid harmine has several neuronal actions.

It acts to slow down the breakdown of monoamine neurotransmitters through inhibition of monoamine oxidase A. Also, it has been shown to specifically inhibit DYRK1A, an enzyme responsible for phosphorylation of tau and thereby may act to slow tau pathology in AD and DS. Nomi fensine is a dopamine reuptake inhibitor originally pre scribed as an anti depressant that has been shown to reverse dopaminergic neurotoxicity and to have beneficial effects in Parkinsons disease. Carba chol is an acetylcholine receptor agonist, but with poor blood brain barrier penetration. The possible appli cation of the other high scoring compounds remains to be determined. Discussion and Conclusions We have collected transcriptional data from diverse plat form architectures corresponding to various species.

By processing the data into effective fold profiles, with the expression levels factored by the average level over the experimental series and defined over a non redundant gene list, we can directly compare transcriptional profiles from arbitrary sources. The fundamental principal underly ing the utility of this approach is that biological effects can be compared through the corresponding transcriptional changes. This idea underlies the CMAP initiative for matching drug to phenotype by querying a database of drug induced transcriptional profiles with a profile defining the phenotype. We have extended this methodology to include potentially all available transcriptional data. In its current version SPIED contains transcriptional profiles for 106,101 arrays covering five platform architectures and three species.

This can be easily extended to include other platforms and species. The results largely confirm the hypothesis that high scoring correlations correspond to similar biological processes. We have presented SPIED results for drug perturbagen induced profile queries and queries derived from disease states. For brevity we focussed on three sets of drug treatment Dacomitinib profiles corresponding to mTOR PI3K, estrogen and HDAC inhibitors.