PMID- 30079978
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20190916
IS  - 1860-7187 (Electronic)
IS  - 1860-7179 (Linking)
VI  - 13
IP  - 19
DP  - 2018 Oct 8
TI  - RASPELD to Perform High-End Screening in an Academic Environment toward the 
      Development of Cancer Therapeutics.
PG  - 2065-2072
LID - 10.1002/cmdc.201800477 [doi]
AB  - The identification of compounds for dissecting biological functions and the 
      development of novel drug molecules are central tasks that often require 
      screening campaigns. However, the required architecture is cost- and 
      time-intensive. Herein we describe the devices and technologies that comprise a 
      Robotics-Assisted Screening Platform for Efficient Ligand Discovery (RASPELD), 
      which we set up in an academic laboratory. RASPELD provides semi-automated 
      high-end screening, and it can be maintained by graduate students. We demonstrate 
      its successful application in biochemical and cellular screens for the 
      identification and validation of bioactive chemical entities as candidate 
      cancer-relevant inhibitors. Specifically, we examined the interaction between a 
      transcription factor, Nrf2, and its key regulator, Keap1. We also examined 
      drug-resistant mutants of the epidermal growth factor receptor (EGFR). Screening 
      campaigns with more than 30 000 compounds were performed in a reasonable period 
      of time. We identified the molecule RSL6586 as a starting point for hit 
      optimization, which is currently ongoing.
CI  - (c) 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Wolle, Patrik
AU  - Wolle P
AD  - Faculty of Chemistry and Chemical Biology, TU Dortmund University, 
      Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.
FAU - Weisner, Jorn
AU  - Weisner J
AD  - Faculty of Chemistry and Chemical Biology, TU Dortmund University, 
      Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.
FAU - Keul, Marina
AU  - Keul M
AD  - Faculty of Chemistry and Chemical Biology, TU Dortmund University, 
      Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.
FAU - Landel, Ina
AU  - Landel I
AD  - Faculty of Chemistry and Chemical Biology, TU Dortmund University, 
      Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.
FAU - Lategahn, Jonas
AU  - Lategahn J
AD  - Faculty of Chemistry and Chemical Biology, TU Dortmund University, 
      Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.
FAU - Rauh, Daniel
AU  - Rauh D
AUID- ORCID: 0000-0002-1970-7642
AD  - Faculty of Chemistry and Chemical Biology, TU Dortmund University, 
      Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180823
PL  - Germany
TA  - ChemMedChem
JT  - ChemMedChem
JID - 101259013
RN  - 0 (Antineoplastic Agents)
RN  - 0 (KEAP1 protein, human)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (Ligands)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Small Molecule Libraries)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Biological Assay
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical/instrumentation/*methods
MH  - Education, Graduate
MH  - ErbB Receptors/antagonists & inhibitors/genetics
MH  - Humans
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - Ligands
MH  - Mutation
MH  - NF-E2-Related Factor 2/metabolism
MH  - Protein Binding/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Robotics/instrumentation/*methods
MH  - Small Molecule Libraries/*pharmacology
OTO - NOTNLM
OT  - cancer
OT  - drug discovery
OT  - hit validation
OT  - initial screen
OT  - medicinal chemistry
EDAT- 2018/08/07 06:00
MHDA- 2019/09/17 06:00
CRDT- 2018/08/07 06:00
PHST- 2018/07/17 00:00 [received]
PHST- 2018/08/07 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2018/08/07 06:00 [entrez]
AID - 10.1002/cmdc.201800477 [doi]
PST - ppublish
SO  - ChemMedChem. 2018 Oct 8;13(19):2065-2072. doi: 10.1002/cmdc.201800477. Epub 2018 
      Aug 23.