PRESENTATION SLIDES & VIDEOS
Despite having more information and technology than at any point in history, drug discovery is becoming harder. It is tempting to believe that there was ‘low hanging fruit’ in the past, and that previous generations had easier to treat diseases, simpler biology and a large number of drug-like leads to optimize. Regardless of the cause, there is now a pressing need to understand fundamental complex biological systems, especially those linked to disease pathology. The most definitive tools for illuminating biology for this are often small molecules, and there is now intense interest in developing, in a cost effective way, potent, well distributed and selective chemical probes, then applying these to understand the role of novel genes, potentially leading to a new medicine.
Underlying the development of chemical probes and drug leads, is what is known from the past, and what general rules can be learnt that are useful in the future. The presentation will detail the background and development of two large, now public domain, chemical biology databases – ChEMBL and SureChEMBL. These databases, in particular ChEMBL have led to the development of many new algorithms for target prediction, chemical library design, etc. Next four examples of data mining of ChEMBL and other public domain data will be described.
1) A framework to anticipate and integrate into compound design processes the effect of mutations in the target – this is of special importance in the area of anti-infective and anti-cancer drugs where resistance is a significant healthcare issue.
2) An analysis of drug properties according to target class for the antibiotics, where differences in physicochemical properties can be correlated in target properties.
3) Addressing the problem of target validation using genetics, which could de-risk the development of chemical tools and leads, and place novel targets into an appropriate therapeutic setting.
4) Is the concept of ‘Druggability’ real, or has it led to restriction in the number of systems that the community is prepared to work on?
Right at the beginning we would like to give our audience a recap of the available potential lying in the ChemAxon portfolio and how these capabilities are assembling into solutions. Ákos Tarcsay, our application scientist will give an introduction to the tools and applied concepts and he will embed them into user’s context concisely to demonstrate how cheminformatics challenges are solved with the help of ChemAxon.
Marvin JS is ChemAxon’s chemical editor web component designed for the wider community. It provides a clean, smart user-oriented interface for quick and convenient drawing of chemical structures and reaction/reactions mechanisms in web pages.
This presentation will focus on the newest development and give a short general overview about the use cases it was designed for.
Discngine Decision is a scientific support platform used to combine and interpret experimental results and speed up decision-making processes. Discngine Decision can gather and analyze data from multiple and heterogeneous data sources like corporate data centers and cloud-hosted databases but also perform on-the-fly data calculations and predictive modeling analysis.
Due to a constant need of distance learning programs, introduction of an e-learning platform and evolution of web technologies, the integration of new chemical drawing editor Marvin JS to systems and applications at UCT, Prague was started approximately 3 years ago.
Allergic contact dermatitis (aka., skin sensitization) accounts for 20% of all contact dermatitis cases and hence has an estimated annual cost up to $200 million. It is also a public health problem, responsible for more than seven million outpatient visits annually. Currently, there are more than 3700 substances that are identified as contact allergens. Traditionally, skin sensitization hazards are assessed using in vivo animal experiments. However, the legislation is increasingly put in place to encourage the replacement of such experiments with non-animal methods. Cosmetic products in the European Union are now banned from using animals for hazard testing. A prohibition is also in place for the sales of products that have been previously tested on animals or that contain ingredients which have undergone such testing following the ban. Multiple tests have been suggested to reflect the current mechanistic understanding of the processes leading to skin sensitization and many framework proposals were reported to guide classification decisions with alternative non-animal data.
We present an implementation for an integrated testing strategy approach previously described by Jaworska et al. The Integrated Testing Strategy (ITS-3) utilizes a Bayesian network to assesses skin sensitization potency by combining information from three validated alternative assays, DPRA, KeratinoSens and h-CLAT as well as in silico predictions for bioavailability to provide a quantitative estimation for skin sensitization potency (a stimulation index = 3; EC3) across a four-category system (Non-, weak, moderate or strong sensitizers). The one-step look-ahead hypothesis was used to calculate the VoI from all network variables which were therefore ranked according to their importance in the decision process as suggested by Jaworska et al. and is used as the methodology to guide testing (i.e., by suggesting the variable (in vitro or in silico) for which its knowledge would maximize information gain about skin sensitization).
The calculated Bayesian factors (BF) serve to correct the imbalance in chemical representation in the training set as well as provide a quantitative assessment of the confidence in prediction. The threshold for strength of evidence suggested by Goodman were used. The posterior probability of chemicals is corrected to reflect the anti-inflammatory effect of Michael acceptors. The decision of whether a compound is considered a direct Michael acceptor for which correction is needed is based on SMARTS patterns.
The deployed web application allows risk assessors to use a web-interface to perform safety assessment for skin sensitization in an interactive manner. As structures are being sketched or entered as SMILES strings, the application calculates in silico parameters for solubility, lipophilicity, partition coefficient and protein binding. It provides instant feedback if chemicals are thought to be out of experiments’ applicability domain and suggests next experiment to be performed in order to achieve the highest value of information. The robust architecture allows the integration of the tool into workflow systems such as KNIME and Pipeline Pilot through he use of application programming interfaces (APIs) or in custom applications.
Similarity of molecular structures is data-set dependent. The DTP’s NC60 panel is a collection of 60 cancerous cell lines maintained by the National Cancer Institute (NCI). Since 1990 tens of thousands of chemical compounds and natural products have been screened against these cells providing a vast repository of molecules for which both toxicity data and structural information are available. In our work, pairwise structural and biological activity similarities were calculated on a set of selected DTP agents to quantify how well structure similarity predicts related patterns in the toxicity data. In total, we found that the capacity of all tested structural metrics are comparable in terms of indicating biological activity similarity.
However, the set of agent pairs displaying both structural and biological activity similarities are slightly distinct in the case of the different metrics. The group of compound pairs exhibiting 3D shape and biological activity but not molecular descriptor based similarities are of special interest: among them, scaffold hopping molecule pairs are expected. The toxicity patterns of these molecule pairs are analogous by definition, they also display analogous 3D shapes as ensured by the 3D shape based similarity, but their core structures are likely to be different because of the dissimilarity in the molecular descriptor based metric. Hence they are likely to exhibit scaffold hopping, an approach defined by similar biological activities of different molecular backbones. Scaffold hopping candidates around FDA approved DTP agents were collected, since a scaffold hopping analogue of an active compound may exhibit better physicochemical and pharmacokinetic properties while retaining the original potency thus providing a new direction for further optimization.
It takes a long and careful process to nurture chemical ideas from concept to a critically evaluated, challenged and understood clinical candidate. From as early as a hand drawn sketch, to as far as a compound with several rounds of assays, Marvin Live is there to assist with the creation, collection and characterisation of chemical ideas. As data integration platform, the array of available tools span phys-chem descriptors, combined metrics like MPO score, 3D overlay and modelling results conducted with KNIME. Use cases of rapid freedom to operate analysis; and SAR by catalog will be shown to ensure that designers can seamlessly exploit the chemical space around their ideas.
How to make better molecules faster is a key challenge in preclinical drug discovery. At Sprint Bioscience we use fragment-based techniques to quickly find high-quality chemical starting points for our small molecule drug discovery projects. Then, we use structure-based drug design to optimize the compounds towards clinical testing.
In this talk, I will illustrate how Marvin Live is used to streamline our collaborative workflows in the medicinal chemistry team – from a design idea to a target molecule ready to be synthesized in the lab.
ChemAxon’s search and database technology includes our JChem Base tool and two cartridges: One running on Oracle, and the other on PostgreSQL. We usually refer to these products as the heart of ChemAxon, since all the search capabilities derive from these tools throughout our software portfolio.
This talk will focus on the latest improvements in JChem PostgreSQL Cartridge.
MadFast is a new innovative product for blazing fast in-memory similarity searches of large chemical sets – processing compound sets with hundreds of millions of sizes.
This presentation will walk viewers through the steps required to get familiar with the three different channels of the tool: its command line interface, the web user interface (UI), and the REST API.
A real-world use case will be demonstrated: a simple similarity-based overlap assessment of molecule sets:
– Import the structures
–Execute exhaustive similarity searches
– Interpret and visualize the results
Merck is at the end of the migration to a new foundation technology for NCEs (Cartridge, Drawing tool and Office-AddOn).
The decision was made to go with ChemAxon Technology (Cartridge, Marvin, JChem for Office). The presentation describes vendor selection, risk analyses, and mitigation plan and the high-level implementation plan. During the migration phase, the need came up to check our research structures for controlled substances. Based on functionality and the experience with the support from ChemAxon, we decided for Compliance Checker (CC) and integrated CC into our application landscape.
At the end of the presentation, we will add a short summary where we are today.
Compliance Checker is a combined software system and content package providing a way to check whether your compounds are controlled according to the laws of the countries of interest.
This presentation shows how chemists and administrators can use the browser-based user interface, and how the RESTful web service API can be used for integration into corporate systems.
ChemAxon’s Biomolecule Toolkit – now extended with an editor, called BioEddie – is a web service-based toolkit to bridge the gap between biology and chemistry for complex biomolecular entities. It provides unambiguous representation at sequence and atomic level for a diverse set of biomolecules such as peptides, oligonucleotides, proteins, antibody drug conjugates, including those containing unnatural and chemically-modified components; thereby allowing their storage, indexing and search within a database.
The toolkit can be applied to extend existing biologics management platforms or to form the basis of a biomolecule registration system. It is capable of mapping specific workflows and business logic for canonicalization, registration and querying.
Biologics research and development is a complex and lengthy process. Many diverse needs are currently satisfied by a variety of tools with nothing to tie them together. Organizations gravitate towards biologics registration, but this means different things to different users.
In this talk, we will discuss how IDBS are leveraging ChemAxon tools to extend capabilities in biologics research and development.
ChemAxon’s consultancy service help clients: evaluate, deploy, adopt, and extend the utility of our informatics within their research processes and internal workflow systems.
This presentation will very briefly give an overview about the scope of the consultancy team. After the introduction, we will focus more on use cases.
The European Lead Factory is an EU-led initiative, part of the IMI program, involving pharmaceutical companies, academic organizations, contract research organizations and public bodies to collaborate on early-stage drug discovery. Part of this initiative is to generate a Joint European Compound Collection (JECC) that can be used for screening. 300,000 compounds were supplied by the pharmaceutical members and a further 200,000 compounds were to be added using novel combinatorial libraries sourced from design proposals from the project partners and external parties.
ChemAxon’s role has been to create a web portal for submission and assessment of proposals for these libraries. This web portal was built by ChemAxon consultancy and is hosted and managed by ChemAxon. This portal has now been in operation for over three years and has been pivotal in generating novel library proposals that have gone on to be synthesized and added to the JECC. As the project draws to a successful close we report on how this was achieved and on some lessons learned.
Data management and the seamless support of the design-production workflows play a key role in the life of a CRO company. No matter if it is about building blocks, libraries, off-the-shelf compounds or custom synthesis, automation is one of the important factors when it comes to a reliable and high-quality service.
The presentation will provide an insight into the library design workflows implemented in KNIME using ChemAxon’s Standardizer, Reactor and calculator tools. A custom-built ELN-LIMS inventory system will also be discussed, demonstrating the role of the advanced structure handling provided by JChem in the data flow of the production system implemented within ComInnex.
We will dive deep into three Compound Registration related topics that are less known, yet interesting to the audience. ChemAxon’s Compound Registration is a system built on a set of web services, aiding users to register molecular structures into a compound database. The registration process spots unique compounds among a set of structures already contained within the database.
The configurability of the registration’s business rules enables flexible definition of uniqueness in accordance with enterprise level requirements. Incoming compound submissions are processed by these business rules, and fully audited registration data is stored for all unique compounds while minimizing the amount of manual curation.
JChem for Office integrates chemical structure handling and visualizing capabilities within a Microsoft Office environment. This presentation features the revamped JChem for Office API that enables easy insertion of structure objects into PowerPoint and Word documents from Java or .NET environment, and can convert all structure objects in a Word document according to a journal style at once. The talk will also show how the redesign of the JChem for Office add-ins helped to significantly reduce the startup time of MS Office applications.
Instant JChem is a desktop application designed for researchers and can be considered as a predecessor of the emerging Plexus Suite. Instant JChem allows you to create, explore, and share chemical and nonchemical data in local and remote databases without additional administration. Instant JChem has a wide and growing range of functionality including customizable database views, integration of library enumeration and dynamic population of columns with singular and combined molecular property and descriptor predictions.
Our research interests focus on compounds that have the potential to overcome multidrug resistance in cancer. Compounds showing paradoxical toxicity against otherwise multidrug resistant cells were first identified in a publicly available database comprising the in vitro toxicity profiles of >40.000 compounds on 60 cancer cell lines (DTP database, NCI). Our aim was to increase the potency of the initial hits by exploring the chemical space around scaffolds identified in the in silico screen.
Commercially available compounds of interest were identified in a vendor database using substructure and similarity searches in Instant JChem (IJC). Non-available and innovative molecules were synthesized. Screening data of biological activity was analyzed by a custom software; IC50 values were imported into IJC to merge biological and chemical data. Structure activity relationships were investigated combining different techniques and tools ranging from “paper-chemistry” to JChem for Excel and the application of Plexus Connect for multivariate analysis. Further IJC functions, especially of JChem for Excel are used for the analysis and visualization of Structure-Activity-Relationships within the datasets.
Plexus Suite is a web-based software package that accesses, displays, searches and analyzes scientific data. Several ChemAxon tools are integrated into the software suite (with additional tools to come) combining our strong chemistry knowledge with all the technical benefits of a browser-based environment. Plexus Suite consists of various tools. Each tool adds specific knowledge to the major display and query tool – Plexus Connect. Currently, three Plexus Suite tools have been released: Plexus Connect, Plexus Design and Plexus Analysis which can be accompanied by other ChemAxon products.
This presentation will focus on several, smaller user stories where the core problem is to find relevant chemical data in various internal and external document repositories. The problem gets even more complicated with the different environments our users need to handle.
Some of the data sits on local machines’ drives, but many colleagues used Dropbox or Google folders to store data. Our new ChemLocator tool will be of a great help in these cases.
ChemCurator is designed to help extracting chemical information from patents, journal articles, and other documents. Combining ChemAxon’s text mining, structure handling and Markush technology, this application can extract and highlight structures within documents, allowing users to interactively extract chemical information or assemble the Markush structures in a semi-automated way. As well as advanced visualization capabilities ChemCurator offers essential functions for validation and manual refining of the automatically extracted chemical information. Besides of a brief functionality overview I will also preset the most important updates of the last year and our future plans.
Chemical structures (of organic compounds) are the basis of the language of chemistry. For those who understand it, it conveys lots of information in terms of molecular and bulk properties, chemical reactivity or biological activity. In today’s era of Big Data, enabling modern exploitation of chemical data requires that it is given in a technologically suitable format – chemical structure format such as, for example, SDF. Here we present and comment on several use cases of ChemCurator, a program that automates retrieval and conversion of chemical data into a suitable structural format.
Analytical laboratory data often involves handling of chemical formulas and structures. Here we present how we facilitate this task by integrating the JChem Plugin in our Seahorse Software Suite and Bio Process Management.
Finnish matriculation examination is the easiest way to apply to the universities. The students usually take the test on their 12th school year. Since 2016 the exam has been carried out electronically and this week MarvinSketch was introduced as a part of the test takers’ environment as one application.
The presentation demonstrates how a user could register molecules using ChemAxon Registration and manage the associated inventory using Mosaic Sample Management software.