Chemical Multiverse: An Expanded View of Chemical Space

Medina-Franco, José L.; Chávez-Hernández, Ana L.; López, Edgar López; Saldívar-González, Fernanda I.

doi:10.1002/minf.202200116

Cited by 47 publications

(42 citation statements)

References 69 publications

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“…In this sense, the combination of several complementary approaches including similarity searching and prediction of ADMET properties, also included in this protocol, has demonstrated the dramatic reduction of false‐positive cases. [ 31 , 32 , 33 , 34 ]…”

Section: Resultsmentioning

confidence: 99%

Consensus Virtual Screening Protocol Towards the Identification of Small Molecules Interacting with the Colchicine Binding Site of the Tubulin‐microtubule System

López

Cerda-Garcı́a-Rojas

Medina‐Franco

2022

Molecular Informatics

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Modification of the tubulin‐microtubule (Tub‐Mts) system has generated effective strategies for developing different treatments for cancer. A huge amount of clinical data about inhibitors of the tubulin‐microtubule system have supported and validated the studies on this pharmacological target. However, many tubulin‐microtubule inhibitors have been developed from representative and common scaffolds that cover a small region of the chemical space with limited structural innovation. The main goal of this study is to develop the first consensus virtual screening protocol for natural products (ligand‐ and structure‐based drug design methods) tuned for the identification of new potential inhibitors of the Tub‐Mts system. A combined strategy that involves molecular similarity, molecular docking, pharmacophore modeling, and in silico ADMET prediction has been employed to prioritize the selections of potential inhibitors of the Tub‐Mts system. Five compounds were selected and further studied using molecular dynamics and binding energy predictions to characterize their possible binding mechanisms. Their structures correspond to 5‐[2‐(4‐hydroxy‐3‐methoxyphenyl) ethyl]‐2,3‐dimethoxyphenol (1), 9,10‐dihydro‐3,4‐dimethoxy‐2,7‐phenanthrenediol (2), 2‐(3,4‐dimethoxyphenyl)‐5,7‐dihydroxy‐6‐methoxy‐4H‐1‐benzopyran‐4‐one (3), 13,14‐epoxyparvifoline‐4’,5’,6’‐trimethoxybenzoate (4), and phenylmethyl 6‐hydroxy‐2,3‐dimethoxybenzoate (5). Compounds 1–3 have been associated with literature reports that confirm their activity against several cancer cell lines, thus supporting the utility of this protocol.

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Section: Resultsmentioning

confidence: 99%

Consensus Virtual Screening Protocol Towards the Identification of Small Molecules Interacting with the Colchicine Binding Site of the Tubulin‐microtubule System

López

Cerda-Garcı́a-Rojas

Medina‐Franco

2022

Molecular Informatics

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“…However, it is not easy to collect, order, and organize such heterogeneous information. In order to enter an era where chemical and biological spaces are integrated, the development of new methodologies is required for assessing chemical and biological similarity and for handling genes, proteins, omics data, and chemical data in a consistent manner [47].…”

Section: Operational Issues and Challengementioning

confidence: 99%

Chemoinformatics and Artificial Intelligence Colloquium: Progress and Challenges to Develop Bioactive Compounds

Bajorath

Chávez-Hernández

Duran‐Frigola³

et al. 2022

Preprint

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We report the main conclusions of the first Chemoinformatics and Artificial Intelligence Colloquium, Mexico City, June 15-17, 2022. Fifteen lectures were presented during a virtual public event with speakers from industry, academia, and non-for-profit organizations. Twelve hundred and ninety students and academics from more than 60 countries. During the meeting, applications, challenges, and opportunities in drug discovery, de novo drug design, ADME-Tox (absorption, distribution, metabolism, excretion and toxicity) property predictions, organic chemistry, peptides, and antibiotic resistance were discussed. The program along with the recordings of all sessions are freely available at https://www.difacquim.com/english/events/2022-colloquium/

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“…From the dataset with 471 compounds associated with DILI reports (available in the Supplementary material: "DB_ConsensusChemSpace_DILI.csv"), hepatotoxicity cell activity and cytochrome inhibition data were constructed and analyzed in their different chemical space representations based on chemical, physicochemical, structural, and in vitro (bioactivity) profile: cytochrome and hepatotoxic cell activity. The implementation of different chemical representations to analyze chemical spaces has been recently termed multiverse chemical space analysis [9].…”

Section: Chemical Space Constructionmentioning

confidence: 99%

“…Since the chemical space depends directly on the descriptors used to define the M-dimensional cartesian space, it is important to mention that it is possible for the coexistence of parallel (or alternative) chemical spaces for the same set of molecules, namely, a multiverse chemical space. Also, it is possible to combine the alternative chemical spaces to create a single "consensus" chemical space [9]. The chemical space application has demonstrated improvement in drug design, making decisions related to the prediction of structureproperties relationships (SPR), side effects, and polypharmacology drug activity, to mention a few of the most recent advances [10].…”

Section: Introductionmentioning

confidence: 99%

Towards uncoding hepatotoxicity of approved drugs through navigation of multiverse and consensus chemical spaces

López-López¹,

Medina-Franco

2022

Preprint

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Drug-induced liver injury (DILI) is the principal reason for failure in developing drug candidates. It is the most common reason to withdraw from the market after a drug has been approved for clinical use. Therefore, a current challenge is enhancing the accuracy of DILI events' predictive models. In this context, data from animal models, liver function tests, and chemical properties could complement each other to understand DILI events better and prevent them. Since the chemical space concept improves decision-making drug design related to the prediction of structure-property relationships, side effects, and polypharmacology drug activity (uniquely mentioning the most recent advances), it is an attractive approach to combining different phenomena influencing DILI events (e.g., individual “chemical spaces”) and exploring all events simultaneously in an integrated analysis of the DILI-relevant chemical space. However, currently, no systematic methods allow the fusion of a collection of different chemical spaces to collect different types of data on a unique chemical space representation, namely "consensus chemical space." This study is the first report that uses the data fusion concept to combine different chemical spaces to facilitate the analysis and prediction of DILIrelated events. The present work remarks the importance of analyzing together in vitro and chemical data (e.g., topology, bond order, atom types, presence of rings, ring sizes, and aromaticity of compounds encoded on RDKIT fingerprints). These properties could be aimed at improving the understanding of DILI events.

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Chemical Multiverse: An Expanded View of Chemical Space

Cited by 47 publications

References 69 publications

Consensus Virtual Screening Protocol Towards the Identification of Small Molecules Interacting with the Colchicine Binding Site of the Tubulin‐microtubule System

Consensus Virtual Screening Protocol Towards the Identification of Small Molecules Interacting with the Colchicine Binding Site of the Tubulin‐microtubule System

Chemoinformatics and Artificial Intelligence Colloquium: Progress and Challenges to Develop Bioactive Compounds

Towards uncoding hepatotoxicity of approved drugs through navigation of multiverse and consensus chemical spaces

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