PASS Biological Activity Spectrum Predictions in the Enhanced Open NCI Database Browser

Abstract

The application of the program PASS (Prediction of Activity Spectra for Substances) to about 250 000 compounds of the NCI Open Database and the incorporation of over 64 million PASS predictions in the Enhanced NCI Database Browser are described. A total of 565 different types of activity are included, encompassing general pharmacological effects, specific mechanisms of action, known toxicities, and others. Application of this Web-based service to prediction of activities of the kinds "Angiogenesis inhibitor," "Antiviral (HIV)", and a set of activities that can be associated with antineoplastic action are reported. For this latter data set, a very substantial enrichment over random selection was found in the PASS predictions. It is shown how the user can conduct complex searches by combining ranges of PASS-predicted probabilities of compounds to be active or to be inactive, respectively, with, e.g., value ranges of physicochemical parameters, presence or absence of particular substructural fragment, and other search criteria.

Inhibition of Toxoplasma gondii and Plasmodium falciparum Infections in Vitro by NSC3852, a Redox Active Antiproliferative and Tumor Cell Differentiation Agent

“…The PASS program had been previously validated for the identification of anticancer and antiretroviral activity in the NCI compound library. Poroikov et al (2003) reported that among 250,000 NCI compounds, 12.5% compounds with a PASS P value ϭ 0.6 exhibited antiretroviral activity in vitro.…”

“…The statistical significance of effects of inhibitors on T. gondii tachyzoite proliferation was evaluated using ANOVA and Dunnett's t-test analyses (PrismGraphPad v. 5). Table I lists 13 small molecule anticancer quinolines from the NCI compound library and a P-value, which is a predictive measure of their antiprotozoan activity obtained from the PASS computer program (Poroikov et al, 2003). We identified these using a 2-step process.…”

Biological spectra analysis: Linking biological activity profiles to molecular structure

“…Obviously, these models must also factor in the variance of molecular property and biological response descriptors based on differences in biological environments (8). Considering the complexity of this requirement, computational solutions that precisely link molecular structure to broad biological response are currently not possible (9,10). We report here an approach to structure-function studies that is based on measurements of the capacity of molecules to interact with the proteome (11).…”

Synthesis, antibacterial studies, and molecular modeling studies of 3,4-dihydropyrimidinone compounds

“…1 Grindstone chemistry pathway for DHPM synthesis specific biological targets. The online version of PASS program was applied for selecting the compounds with desirable and without toxicity of biological activities among the 250, 000 compounds from NCI database [23,24]. The NCI database includes drugs, drug candidates, leads, and toxic substances.…”

“…The structure descriptor Multilevel Neighbourhood of Atom (MNA) is used in PASS to illustrate the chemical structures. Depending on the statistics of MNA descriptors of the training set descriptors for active and inactive compounds from the original training set, two probabilities are calculated for each activity: Pa the probability of the compound being active and Pi the probability of being inactive [24]. The Pa and Pi values vary from 0 to 1, and Pa+Pi<1, since these probabilities are calculated independently.…”