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Gene-signature-derived IC50s/EC50s reflect the potency of causative upstream targets and downstream phenotypes.
Renner, Steffen; Bergsdorf, Christian; Bouhelal, Rochdi; Koziczak-Holbro, Magdalena; Amati, Andrea Marco; Techer-Etienne, Valerie; Flotte, Ludivine; Reymann, Nicole; Kapur, Karen; Hoersch, Sebastian; Oakeley, Edward James; Schuffenhauer, Ansgar; Gubler, Hanspeter; Lounkine, Eugen; Farmer, Pierre.
Afiliación
  • Renner S; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research (NIBR), Basel, 4056, Switzerland. steffen.renner@novartis.com.
  • Bergsdorf C; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research (NIBR), Basel, 4056, Switzerland.
  • Bouhelal R; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research (NIBR), Basel, 4056, Switzerland.
  • Koziczak-Holbro M; Musculoskeletal, NIBR, Basel, Switzerland.
  • Amati AM; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research (NIBR), Basel, 4056, Switzerland.
  • Techer-Etienne V; Department of Chemistry & Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
  • Flotte L; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research (NIBR), Basel, 4056, Switzerland.
  • Reymann N; Musculoskeletal, NIBR, Basel, Switzerland.
  • Kapur K; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research (NIBR), Basel, 4056, Switzerland.
  • Hoersch S; NIBR Informatics, NIBR, Basel, Switzerland.
  • Oakeley EJ; NIBR Informatics, NIBR, Basel, Switzerland.
  • Schuffenhauer A; ASI, NIBR, Basel, Switzerland.
  • Gubler H; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research (NIBR), Basel, 4056, Switzerland.
  • Lounkine E; NIBR Informatics, NIBR, Basel, Switzerland.
  • Farmer P; Chemical Biology & Therapeutics, NIBR, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Sci Rep ; 10(1): 9670, 2020 06 15.
Article en En | MEDLINE | ID: mdl-32541899
Multiplexed gene-signature-based phenotypic assays are increasingly used for the identification and profiling of small molecule-tool compounds and drugs. Here we introduce a method (provided as R-package) for the quantification of the dose-response potency of a gene-signature as EC50 and IC50 values. Two signaling pathways were used as models to validate our methods: beta-adrenergic agonistic activity on cAMP generation (dedicated dataset generated for this study) and EGFR inhibitory effect on cancer cell viability. In both cases, potencies derived from multi-gene expression data were highly correlated with orthogonal potencies derived from cAMP and cell growth readouts, and superior to potencies derived from single individual genes. Based on our results we propose gene-signature potencies as a novel valid alternative for the quantitative prioritization, optimization and development of novel drugs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Agonistas Adrenérgicos beta / Perfilación de la Expresión Génica / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Agonistas Adrenérgicos beta / Perfilación de la Expresión Génica / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido