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Royal Society of Chemistry Renews Partnership with ACD/Labs to Continue Providing Industry-Leading Data to Worldwide Research Community
Jul 26, 2018
ACD/Labs
Press Release
Read Abstract
ACD/Labs algorithms will continue to equip ChemSpider with physicochemical property values and chemical nomenclature following ten year milestone.
Royal Society of Chemistry Renews Partnership with ACD/Labs to Continue Providing Industry-Leading Data to Worldwide Research Community


Evaluating Physicochemical Model Predictions Using a Web-Based Percepta Client
Jun 14, 2018
D. Stanton (Procter & Gamble)
Webinar
Read Abstract
Procter & Gamble employs the Percepta platform to replace physicochemical property calculations made through physical laboratory experiments with virtual experiments. The software helps chemists and formulators to work more efficiently, and assists in the decision-making process. In this presentation David explains how P&G scientists employ Percepta in divining applicability domains for physicochemical prediction models, and in developing more complex models to estimate the properties of mixtures.
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A Web-Based Informatics Platform for PhysChem/ADME/Tox Property Predictions
May 27, 2018
A. Sazonovas, K. Lanevskij, R. Didziapetris
Poster
May 27, 2018, International Conference on Chemical Structures
Read Abstract
Percepta Portal is a browser-based solution that builds upon the well established components of ACD/Percepta software. It uses the same reliable predictive algorithms for a multitude of physicochemical, ADME, and safety-related properties, powerful data mining, visualization, compound profiling and risk assessment capabilities. It also includes ACD/Structure Design Engine for generating libraries of virtual analogs compatible with the desired characteristics. Percepta Portal combines these features with flexible network-based deployment, raising software interactivity to a new level and offering some exciting features.
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A Comprehensive Evaluation of ACD/LogD on a Pharmaceutical Compound Set
May 27, 2018
A. Sazonovas, K. Lanevskij, R. Didziapetris
Poster
May 27, 2018, International Conference on Chemical Structures
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Lipophilicity, which is often expressed in terms of 1-octanol/water partitioning coefficient logP, or the corresponding pH-dependent distribution coefficient logD, is one of the key physicochemical characteristics of any new drug candidates, as it has a major influence on a variety of the compounds’ properties constituting their ADME, pharmacokinetic, and drug safety profiles. Widely available in silico tools for predicting these properties are mostly based on experimental data for simple organic chemicals and marketed drugs. Consequently, as drug discovery projects are moving to increasingly novel regions of chemical space, utility of existing methods becomes more and more questionable. In several previously published evaluation studies1,2, the mean logP prediction error for in house compound libraries of pharmaceutical companies was shown to exceed 1 log unit by almost all methods. Prediction of logD is even more challenging, as it requires accurate knowledge of both logP of neutral form and distribution of ionic forms of the compound in the relevant pH range.
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Relative toxicological ranking of eight polybrominated diphenyl ether congeners using cytotoxicity, chemical properties and exposure data
Feb 26, 2017
S. Tait, M. Perugini, C. La Rocca
Article
Third-Party Reference
Food and Chemical Toxicology
Polybrominated diphenyl ethers are widely used flame retardants which persist and diffuse in the environment thus entering the food chain. Eight congeners, most relevant for human exposure (BDE-28, 47, 99, 100, 153, 154, 183 and 209), were analyzed in vitro and in silico to derive a relative toxicological ranking.

Cytotoxicity was assessed on human liver (HepG2) and colon (DLD-1) cell lines, by three assays (MTS, ATP and DNA content) in a range of realistic concentration (1pM - 10 nM). Jejunum and Caco-2 passive absorptions were calculated in silico. Exposure estimates were calculated using EFSA database. By ToxPi we integrated the overall data.

No reduction of DNA content was observed, supporting absence of cytotoxicity. Otherwise, hormetic effects were exerted by all the congeners, except BDE-183. BDE-28, 47, 99, 100 differently affected the ATP content inducing a dose-related increase in HepG2 and depletion in DLD-1. Jejunum coefficients did not differ among congeners, whereas a higher Caco-2 coefficient indicates rapid absorption of BDE-28.

ToxPi relative rankings support the toxicological relevance of BDE-153 and 28 congeners for their potential hazard; the inclusion of exposure data in young and adult populations shifted BDE-209 and BDE-47 as top ranked due to their widespread occurrence in the diet.
Food and Chemical Toxicology. 108 (Part A): 74–84, 2017


Determination of acid dissociation constants (pKa) of cephalosporin antibiotics: Computational and experimental approaches
Nov 18, 2016
A.R. Ribeiro, T.C. Schmidt
Article
Third-Party Reference
Chemosphere
Cefapirin (CEPA) and ceftiofur (CEF) are two examples of widely used veterinarian cephalosporins presenting multiple ionization centers. However, the acid dissociation constants (pKa) of CEF are missing and experimental data about CEPA are rare. The same is true for many cephalosporins, where available data are either incomplete or even wrong. Environmentally relevant biotic and abiotic processes depend primordially on the antibiotic pH-dependent speciation. Consequently, this physicochemical parameter should be reliable, including the correct ionization center identification. In this direction, two experimental techniques, potentiometry and spectrophotometry, along with two well-known pKa predictors, Marvin and Percepta, were used to study the macro dissociation constants of CEPA and CEF. Additionally, the experimental dissociation constants of 14 cephalosporins available in the literature were revised, compiled and compared with data obtained in silico. Only one value was determined experimentally for CEF (2.68 ± 0.05), which was associated to the carboxylic acid group deprotonation. For CEPA two values were obtained experimentally: 2.74 ± 0.01 for the carboxylic acid deprotonation and 5.13 ± 0.01 for the pyridinium ring deprotonation. In general, experimentally obtained values agree with the in silico predicted data (Percepta RMSE: 0.552 and Marvin RMSE: 0.706, n = 88). However, for cephalosporins having imine and aminothiazole groups structurally close, Marvin presented problems in pKa predictions. For the biological and environmental fate and effect discussion, it is important to recognize that CEPA and CEF, as well as many other cephalosporins, are present as anionic species in the biologic and environmentally relevant pH values of 6–7.5.
Chemosphere. 169:524–533.


A simple approach to multifunctionalized N1-alkylated 7-amino-6-azaoxindole derivatives using their in situ stabilized tautomer form
Oct 13, 2016
N.T. Tzvetkov, B. Neumann, H. Stammler, L. Antonov
Article
Third-Party Reference
Tetrahedron
A simple approach for the synthesis of multifunctionalized N1-alkyl 7-amino-6-azaoxindole derivatives was developed and investigated. Formation of 5-amino- and 7-amino-6-aza-2-oxindoles 12a and 13a, respectively, was achieved using an intramolecular reductive cyclization as a key step. Subsequent alkylation of the pyrrole N1 atom in 12a led to the desired N1-alkylated compounds 22a–24 comprising different functionalities. Alkylation of 5-amino-substituted regioisomer 13a under the same conditions as used for 12a did not resulted in N1-alkylated products. To find a plausible explanation for the observed differences in reactivity, we investigated the possible tautomers of 12a and 13a and the distribution of their neutral and ionized forms in a gas phase. The relevant physicochemical properties of compounds 12a and 23 were determined.
Tetrahedron, 72(41): 6455-66, 2016.


ACD/Labs Announces Updates to its Informatics Software
Oct 12, 2016
ACD/Labs
Press Release
Read Abstract
V2016.1 of ACD/Spectrus and Percepta delivers improved knowledge sharing and data-driven decision support for R&D organizations.
ACD/Labs Announces Release of Updated Software


ACD/Portal Technology - Bringing ACD/Labs' Percepta Capabilities to a New Level
Sep 05, 2016
A. Sazonovas, K. Lanevskij
Poster
Sep 04, 2016, EuroQSAR
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Physicochemical Classification Analysis of HERG Inhibitor Specificity
Sep 05, 2016
R. Didziapetris, K. Lanevskij
Poster
Sep 04, 2016, EuroQSAR
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Retention modelling in hydrophilic interaction chromatography (HILIC)
Jun 23, 2016
P. Petersson, M. Euerby, K. Kassam, A. Van Wyk, S. Bhal, and I. Oshchepkova
Poster
Jun 19, 2016, HPLC
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Hydrophilic Interaction Chromatography (HILIC) has seen an exponential growth in use as a complimentary separation technique to Reversed-Phase Chromatography (RPC) in recent decades. HILIC may show improved retention of polar molecules such as drug compounds and their metabolites and increased sensitivity when using electrospray ionization mass spectrometry (ESI-MS) due to the volatile nature of the acetonitrile enriched eluent relative to RPC. Sample preparation is also greatly simplified in bioanalysis where the acetonitrile enriched supernatant from protein precipitations can be directly injected onto the HILIC column without any need for evaporation and reconstitution.

HILIC uses hydrophilic stationary phase with reversed phase type eluents. The separation mode of HILIC is more complicated than RPC due to a multi-retention mechanism that may contribute to the overall retention of analytes. The aim of this work was to gain a better understanding of the retention behaviour of: a range of acidic, basic, quaternary ammonium salts; and polar neutral analytes on acidic, basic and neutral stationary phases as a function of a range of HILIC operating parameters such as MeCN content, buffer concentration, pH, and temperature.

A number of both pre-existing and newly developed HILIC retention models were assessed for their ability to predict retention as a function of the HILIC operating parameters using a commercially available retention modelling program (ACD/LC Simulator).

The applicability of these models has been shown in both two dimensional isocratic and one dimensional gradient separations for a wide range of analytes with varying physicochemical properties for each of the three stationary phases investigated. The accuracy of prediction for both retention time and peak width accuracy was observed to be comparable to standard RPC retention modelling, but unfortunately it was discovered that gradient modelling could not be used to predict HILIC isocratic conditions or vice versa. A statistical approach was followed to produce a relative ranking of the importance of HILIC operating parameters on the selectivity and retention of the models. The ranking observed was as follows: the nature of the stationary phase > mobile phase pH (i.e., pH 3-6 mainly effecting the ionization of the analyte) > buffer concentration = organic content > temperature. An understanding of these relative importances should prove valuable to chromatographers in the rational design of robust HILIC method development strategies.

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A New Approach to the Automated Identification of Metabolites in Multi-Vendor Datasets
Mar 09, 2016
R. Lee, V. Lashin, A. Paramonov, A. Sakharov
Poster
Mar 06, 2016, PITTCON
Read Abstract
For scientists involved in the study of drug metabolism the challenge of accurately and rapidly identifying metabolites is met using a variety of LC/MS techniques and software packages. While most instruments vendors offer software to assist in the identification of metabolites, they are a hindrance in a multi-vendor laboratory, where they lack the flexibility and customization required. Most users have to then resort to purchasing additional software and typically use Microsoft Excel to complete their workflow.
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University of Lyon Researchers Leverage ACD/Labs' Percepta in Search of Green Rocket Fuel
Jan 12, 2016
ACD/Labs
Press Release
Read Abstract
ACD/Labs, a Toronto-based chemistry software company, today announced that for the past three years professor Raphael Terreux of the University of Lyon has relied on the Percepta Platform for a collaborative research project investigating new, environmentally friendly high energy materials. Since leveraging the full suite of Percepta toxicity and ADME predictors, professor Terreux's team has been able to uncover new findings about the application of chemicals used in rocket propellants and explosives. In doing so, the research program hopes to identify a more ecological approach to these harmful materials.
University of Lyon Researchers Leverage ACD/Labs Percepta in Search of Green Rocket Fuel - January 2015


ACD/Labs Announces Release of Updated Software
Jan 29, 2015
ACD/Labs
Press Release
Read Abstract
ACD/Labs, a leading cheminformatics company, today announced the release of their Version 2015 software. Version 2015 builds upon the capabilities of the Spectrus and Percepta platforms. Since their market introduction in 2012, and based on the 20 years of ACD/Labs expertise in the chemistry software market, these two platforms enable organizations to extract results and decisions from data more efficiently, and share knowledge more effectively.
ACD/Labs Announces Release of Updated Software - Jan 2015


Estimation of the chemical-induced eye injury using a weight-of-evidence (WoE) battery of 21 artificial neural network (ANN) c-QSAR models (QSAR-21): Part I: Irritation potential
Dec 08, 2014
R.P. Verma, E.J. Matthews (US-FDA)
Article
Third-Party Reference
Regulatory Toxicology and Pharmacology
Evaluation of potential chemical-induced eye injury through irritation and corrosion is required to ensure occupational and consumer safety for industrial, household and cosmetic ingredient chemicals. The historical method for evaluating eye irritant and corrosion potential of chemicals is the rabbit Draize test.
R.P. Verma, E.J. Matthews. (2015). Regul Toxicol Pharmacol., 71(2):331-6.


The Use of Percepta in the Concept of Regulatory Compliance
Jun 11, 2014
P. Japertas
Presentation
Jun 10, 2014, ACD/Labs European Symposium on Laboratory Intelligence
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The University of Paris Selects Percepta Software to Enhance Teaching and Research into Pharmaceuticals
Dec 16, 2013
ACD/Labs
Press Release
Read Abstract
The Université Paris-Sud (France), School of Pharmacy, has selected ACD/Labs' ADME, Toxicity, and PhysChem predictors on the Percepta Platform, to enable in silico evaluation of pharmaceutical substances and research compounds.
The University of Paris Selects ACD/Labs Percepta Software to Enhance Teaching and Research into Pharmaceuticals - Dec 2013


CIME: Compound Idea Management and Evaluation - Customizing of Percepta as integral Part within CIME
Jun 20, 2013
M. Krug (Merck)
Presentation
Jun 19, 2013, ACD/Labs Symposium on Laboratory Intelligence (EUM)
Read Abstract
Describing the process of customization of Percepta in the scope of our CIME Project. After a short description of the CIME Project itself, info about the decision process of selecting Percepta will be given. Customization as far as it already done will be outlined along with work in progress and planed collaboration for further enhancements.
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Translating Favorable ADME Profile of a Lead Compound into Virtual Analogs in Restricted Physicochemical Space
Jun 19, 2013
P. Japertas, R. Kubilius, A. Sazonovas, K. Lanevskij
Poster
Jun 19, 2013, ACD/Labs Symposium on Laboratory Intelligence (EUM)
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The Challenge of Data Management in the Modern Laboratory—And Modern Responses to Those Challenges
Apr 14, 2013
P. Wheeler
Presentation
Apr 14, 2013, ENC NMR Software Symposium
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Improving the prediction of drug disposition in the brain
Jan 08, 2013
K. Lanevskij, P. Japertas, and R. Didziapetris
Article
Review
Expert Opinion on Drug Metabolism & Toxicology
Introduction: Ability to cross the blood-brain barrier is one of the key ADME characteristics of all drug candidates regardless of their target location in the body. While good brain penetration is essential for CNS drugs, it may lead to serious side effects in case of peripherally-targeted molecules. Despite a high demand of computational methods for estimating brain transport early in drug discovery, achieving good prediction accuracy still remains a challenging task.

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Merck Germany to Deploy Percepta Enterprise Server
Dec 18, 2012
ACD/Labs
Testimonial
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Merck Germany has made a decision to deploy Percepta Enterprise software at their Research facilities in Germany and North America.
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Translating the Favorable ADME Profile of a Lead Compound Into Virtual Analogs in Restricted Physicochemical Space
Sep 03, 2012
P. Japertas, et al.
Poster
Aug 19, 2012, ACS Fall
Sep 02, 2012, EFMC-ISMC
Read Abstract
Full list of Authors: Pranas Japertas; Rytis Kubilius; Andrius Sazonovas; Kiril Lanevskij
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ACD/Labs becomes an associate partner of Open PHACTS project
May 22, 2012
ACD/Labs
Press Release
ACD/Labs becomes an associate partner of Open PHACTS project - May 2012


In-silico techniques in lead optimization—perspectives for rational use
May 20, 2012
Pranas Japertas, Andrius Sazonovas, Kiril Lanevskij
Poster
May 20, 2012, National Medicinal Chemistry Symposium
Read Abstract
Despite constant advances in the QSAR field, computational approaches in general still fail to meet the high expectations associated with their use. In this work we attempt to re-assess the role of various in-silico tools in building an effective lead optimization strategy.

The major issue with most in-silico models available up to date is that they are 'statistics driven' and have been developed with the only pursuit of the best possible fit in mind. At the same time it is usually not taken into account that many of the analyzed properties are governed by the most basic physicochemical characteristics of the compounds, such as ionization, lipophilicity, molecular size, or hydrogen bonding potential. In this work, we demonstrate that this set of parameters suffices for devising accurate models of intestinal absorption and passive permeation across the blood-brain barrier. Moreover general physicochemical trends are observed even for the properties involving protein-ligand interactions (P-gp, hERG). The key advantage of simple physicochemical models is their interpretability. Not only they produce an estimate of the property value for a compound, but also provide a mechanistical insight that has the potential to guide lead optimization in the desired direction. In our opinion, a rational strategy of lead optimization should aim at achieving balanced physicochemical profiles of candidate compounds that would translate into favorable ADME properties.

Another aspect covered in this work is the phenomenon of 'activity cliffs'. It manifests as local anomalies when small structural changes lead to disproportionally large changes in observed effects. The issue could be potentially resolved by employing advanced modeling techniques, such as pairwise QSAR. Additional inclusion of target affinity data in the simple ADME/Tox profiling analysis is introduced next as a natural extension of all above concepts. Available potency data for the considered compound series could be utilized with the help of automated Hansch and Free-Wilson type analysis (Auto-SAR approach). Analog generation combined with automated modeling has the potential to suggest most promising candidates.

The factors that will impact the commercial fate of a particular analogue are not limited by its potency and ADME/Tox profile. There are also a number of aspects that are not associated with compound’s suitability to be used as a drug, namely synthetic feasibility and patentability prospects. The possibilities of their assessment using cheminformatics approaches (such as comparison of substructures of different sizes in the analyzed compounds with the ones in available chemistry) are also overviewed in this work.
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Translating Favorable ADME Profile of a Lead Compound into Virtual Analogs in Restricted
Apr 19, 2012
Pranas Japertas, Rytis Kubilius, Andrius Sazonovas, Kiril Lanevskij
Poster
Apr 19, 2012, PhysChem Forum
Read Abstract
The main idea lying behind our approach is that many considered properties are governed by basic physicochemical parameters, such as ionization, lipophilicity, or molecular size. We have devised simple, yet accurate physicochemical models of intestinal absorption and passive permeation across the BBB, as well as general physicochemical rules that hold, even for protein-ligand interactions (P-gp, hERG inhibitor specificity). Changing parameter values may have distinct, even opposite effects on different ADME properties, and the impact of a particular parameter may depend on the allowed variation ranges of other parameters. Using the cumulative output of available predictive models enables us to account for the multitude of possible effects and identify the regions in physicochemical space that are most likely occupied by analogs with the needed combination of ADME properties. Advanced techniques are also applied to improve selection of substituents fitting within these regions, including custom Hammett equations for estimating the mutual effects of the core molecule and the modified substituent on the analog's pKa. The presented methods coupled with automatic analog generation in accordance with the imposed physicochemical restrictions make our software platform a valuable tool to guide drug discovery projects towards the most promising candidates.
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In silico test battery for rapid evaluation of genotoxic and carcinogenic potential of chemicals
Mar 25, 2012
K. Lanevskij, L. Juska, J. Dapkunas, A. Sazonovas, P. Japertas, R. Didziapetris
Poster
Mar 25, 2012, ACS Spring
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This work is an extension of our previous study focusing on computational assessment of genotoxic impurities in drug products. Our new approach relies on a battery of probabilistic QSAR models supplemented by a knowledge-based expert system that identifies structural fragments potentially responsible for hazardous activity. The analysis was based on experimental data obtained from FDA, and involved 21 endpoints corresponding to different mechanisms of toxic action: mutagenicity, clastogenicity, carcinogenicity, etc. Probabilistic models were derived using GALAS (Global, Adjusted Locally According to Similarity) modeling methodology developed in our group. The updated list of alerting groups contained 70 distinct substructures. The expert system was highly sensitive, recognizing >90% of potent carcinogens, as classified by FDA. Sensitivity of probabilistic GALAS models ranged from 60% to 93%, whilst maintaining high (>80%) specificity of predictions. These results show that the described computational platform ensures sufficient prediction accuracy for rapid genotoxicity/carcinogenicity profiling of various chemicals.
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Classification of drugs by CNS access: An insight from quantitative blood-brain transport characteristics
Mar 25, 2012
K. Lanevskij, P. Japertas, R. Didziapetris
Poster
Mar 25, 2012, ACS Spring
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The ultimate goal of QSAR analysis focusing on blood-brain barrier penetration is the ability to discriminate between CNS active and inactive molecules. The objective of the current study was to establish the relationship between quantitative blood-brain transport parameters and qualitative data indicating whether the compound penetrates into the brain efficiently enough to exhibit central action. Two quantitative characteristics were considered: brain/plasma equilibration rate, and the extent of brain/plasma partitioning at equilibrium (logBB). Analysis of a diverse data set consisting of >1500 compounds from World Drug Index database with experimentally assigned brain penetration categories revealed that a linear combination of the above mentioned parameters allowed classifying drugs by CNS access with 94% overall accuracy. Furthermore, the devised classification score well correlated with unbound brain/plasma partitioning coefficient (logKp,uu), which is recognized as an unambiguous determinant of brain exposure. The obtained results confirm the validity of the proposed classification approach.
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Predicting Genotoxic and Carcinogenic Risk of Pharmaceutical Impurities
Feb 27, 2012
ACD/Labs
Flyer
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ACD/Labs Releases Percepta at AAPS 2011
Oct 26, 2011
ACD/Labs
Press Release
Oct 23, 2011, AAPS—American Association of Pharmaceutical Scientists
ACD/Labs Releases ACD/Labs Percepta at AAPS 2011 - October 2011