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tarGET iD

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In vivo protein target identification / target deconvolution via chemical proteomics as a facilitating tool for phenotype based drug discovery.

www.j-vomacka.com

Veröffentlicht in: Gesundheit & Medizin
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tarGET iD

  1. 1. tarGETiDtarget identification strategy
  2. 2. The chance of phenotype based drug discovery. Phenotype based drug discovery offers the opportunity to screen active compounds directly with complex biological systems. Whole cells can be used instead of in vitro protein assays. An increased focus on phenotype based screening will help to develop innovative first-in-class drugs and will contribute to lower project attrition rates. The challenge. Mechanism of action and direkt protein targets of phenotype based screening hits are initially unknown. 2 1 Swinney, D.C., Phenotypic vs. target-based drug discovery for first-in-class medicines. Clin Pharmacol Ther, 2013. 93(4): p. 299-301. 2 Swinney, D.C. and J. Anthony, How were new medicines discovered? Nat Rev Drug Discov, 2011. 10(7): p. 507-519. 3 Kotz, J., Phenotypic screening, take two. Science–Business eXchange, 2012. 5(15): p. 1-3.
  3. 3. 3 How can chemical proteomics help? By phenotypic screening active compounds with a potentially unique mode of action (first-in-class) are identified. With chemical proteomics the relevant protein interaction partner(s) in whole cells can be determined. After a sucessfull target identification one can proceed with a regular target based drug development process (best-in-class). phenotype based drug discovery target based drug development 1 Swinney, D.C., Phenotypic vs. target-based drug discovery for first-in-class medicines. Clin Pharmacol Ther, 2013. 93(4): p. 299-301. 2 Swinney, D.C. and J. Anthony, How were new medicines discovered? Nat Rev Drug Discov, 2011. 10(7): p. 507-519. 3 Kotz, J., Phenotypic screening, take two. Science–Business eXchange, 2012. 5(15): p. 1-3.
  4. 4. 4 The benefits of knowing the protein interaction partners. • Chemical structure optimization of a screening hit based on crystal structure-guided rational design. • New active structures by target-based high throughput screening. • Better understanding of the toxicology of a candidate. • Off-target profile for priorization of projects at an early development stage.
  5. 5. 5 Target identification technology. Starting point. Small molecule causing a desired effect in human or microbial cell culture. Design of a chemical probe. A derivative of the active compound is synthesized: The chemical probe. Changes of the chemical structure ideally should have only a minimal effect on the biological activity. active compound chemical probe
  6. 6. 6 Target identification technology. target protein(s) interaction partners of active compound cell lysis biotin / avidin enrichment quantitative MS analysis covalent bond formation by UV irradiation labeling of whole cells chemical probe
  7. 7. 7 Target identification technology. Target identification process. Cells are cultured and incubated with the chemical probe bearing a photoactivatable moiety. Covalent binding to the protein targets is then achieved by UV irradiation. After cell lysis a biotin tag is attached to the probe. Target proteins are enriched with the help of avidin beads. Quantitative mass spectrometric analysis of probe treated vs. control samples finally reveals the targets.
  8. 8. 8 Jan Vomacka, a short CV. Jan Vomacka, geb. 14.01.88
  9. 9. 9 Techniche Universität München 10/2008 - 05/2013 Chemistry, B.Sc. and M.Sc. since 06/2013 Chemistry, PhD student AVIRU GmbH 01/2013 - 12/2014 Anti-virulence drug development (MRSA). tarGET iD (seed phase) 01/2015 - 05/2015 Target identification via chemical proteomics.
  10. 10. What I offer. experience with: • chemical proteomics • assay development • target identification (deconvolution) and validation • phenotype based drug development (anti-infectives, MRSA) 10
  11. 11. What I seek. • challenges with impact on pharmaceutical industry • teamwork • project management • intrapreneurship • trust-based working hours • personal responsibility 11
  12. 12. Jan Vomacka www.j-vomacka.com vomacka@me.com / +49 160 7882820 Gowirichweg 6a / D-85748 Garching

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