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Correlation and cluster analysis of immunomodulatory drugs based on cytokine profiles
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Redoxis AB/ProNoxis AB, Lund, Sweden / Wallner Medicinal Chemistry AB, Göteborg, Sweden. (Infektionsbiologi, Infection Biology)ORCID iD: 0000-0002-2812-8255
Redoxis AB/ProNoxis AB, Lund, Sweden.
Redoxis AB/ProNoxis AB, Lund, Sweden.
Redoxis AB/ProNoxis AB, Lund, Sweden.
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2018 (English)In: Pharmacological Research, ISSN 1043-6618, E-ISSN 1096-1186, Vol. 128, p. 244-251Article in journal (Refereed) Published
Abstract [en]

Drug discovery is a constant struggle to overcome hurdles posed by the complexity of biological systems. One of these hurdles is to find and understand the molecular target and the biological mechanism of action. Although the molecular target has been determined, the true biological effect may be unforeseen also for well-established drugs. Hence, there is a need for novel ways to increase the knowledge of the biological effects of drugs in the developmental process. In this study, we have determined cytokine profiles for 26 non-biological immunomodulatory drugs or drug candidates and used these profiles to cluster the compounds according to their effect in a preclinical ex vivo culture model of arthritis. This allows for prediction of functions and drug target of a novel drug candidate based on profiles obtained in this study. Results from the study showed that the JAK inhibitors tofacitinib and ruxolitinib formed a robust cluster and were found to have a distinct cytokine profile compared to the other drugs. Another robust cluster included the calcineurin inhibitors cyclosporine A and tacrolimus and the protein kinase inhibitors fostamatinib disodium and sotrastaurin acetate, which caused a strong overall inhibition of the cytokine production. The results of this methodology indicate that cytokine profiles can be used to provide a fingerprint-like identification of a drug as a tool to benchmark novel drugs and to improve descriptions of mode of action.

Place, publisher, year, edition, pages
2018. Vol. 128, p. 244-251
Keywords [en]
Clustering, Cytokines, Immunosuppressive, PCA
National Category
Pharmacology and Toxicology
Research subject
Infection Biology; INF502 Biomarkers
Identifiers
URN: urn:nbn:se:his:diva-14564DOI: 10.1016/j.phrs.2017.10.012ISI: 000435626500025PubMedID: 29079427Scopus ID: 2-s2.0-85032948174OAI: oai:DiVA.org:his-14564DiVA, id: diva2:1163526
Projects
A novel framework for facilitating drug discovery
Funder
Carl Tryggers foundation , CTS15:232Available from: 2017-12-07 Created: 2017-12-07 Last updated: 2018-07-12Bibliographically approved

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Wallner, Fredrik K.Tilevik, Andreas

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