SimilarityLab: Molecular Similarity for SAR Exploration and Target Prediction on the Web

Steven Shave,Manfred Auer

doi:10.3390/pr9091520

Abstract

Exploration of chemical space around hit, experimental, and known active compounds is an important step in the early stages of drug discovery. In academia, where access to chemical synthesis efforts is restricted in comparison to the pharma-industry, hits from primary screens are typically followed up through purchase and testing of similar compounds, before further funding is sought to begin medicinal chemistry efforts. Rapid exploration of druglike similars and structure–activity relationship profiles can be achieved through our new webservice SimilarityLab. In addition to searching for commercially available molecules similar to a query compound, SimilarityLab also enables the search of compounds with recorded activities, generating consensus counts of activities, which enables target and off-target prediction. In contrast to other online offerings utilizing the USRCAT similarity measure, SimilarityLab’s set of commercially available small molecules is consistently updated, currently containing over 12.7 million unique small molecules, and not relying on published databases which may be many years out of date. This ensures researchers have access to up-to-date chemistries and synthetic processes enabling greater diversity and access to a wider area of commercial chemical space. All source code is available in the SimilarityLab source repository.

Highlights

Academic groups running primary screens rely heavily on strong preliminary results to build a case for further funding to progress their drug and medicines discovery efforts
ReSsiumltislarityLab presents a fast, user-friendly interface for fast molecular similarity calculatSioimnsil(aSreiteyLFaigbuprrees2e).nWts aithfasatn, uesmerp-fhraiesnisdolyninspteerefdacaenfodrnfaesatrminoslteacnutlarressiumltisl,arititiysceanlcvui-lsaiotinoendst.yWLaibthwanillepmlapyhaasims oajnorspreoeled oanndnnoet aornilnystraenstearercshultbsu, titailssoentveiasciohninegd, tahllaotwSiinmgilalarritgyeLgabrowupilsl pthlaeyaabmiliatyjortoropleroognrensost cohnelymrinesfeoarmrchatbicusteaxlspoertiemacehnitnsg,raeltlroiewviinngg lcaormgepgoruonudpsswthheicahbialriteythtoenpruosgerdesasscihnepmutintfooarmvaatriicestyexopf edriifmfeernentst, troeotrlise,vminogdecolsmapnodusnimdswulhaitciohnasr.e used as input to a variety of different tools, models and simulations
It is hoped that SimilarityLab will be used to capitalize on results from primary screens in academia, allowing SAR exploration by non-specialists without access to computational chemists or cheminformaticians

Summary

Introduction

Academic groups running primary screens rely heavily on strong preliminary results to build a case for further funding to progress their drug and medicines discovery efforts. We wish to highlight our most recently developed web-service, SimilarityLab (https://similaritylab.bio.ed.ac.uk accessed on 5 June 2021) [12], giving all researchers in the field a quick way to source and purchase similar compounds which are mostly used to explore SAR around their own hit compounds, as well as those from the literature (see Figure 1). SimilarityLab makes extensive use of the USRCAT [13] 3D molecular similarity measure to query a local, processed version of the eMolecules database [14], currently containing over 12.7 million commercially available, unique druglike small molecules.

Results

Conclusion