Gerhard Ecker

Last updated
Gerhard F. Ecker
Born
NationalityAustrian
Known for Medicinal Chemistry
Pharmacoinformatics
Open PHACTS [1]
Scientific career
Institutions University of Vienna
Website pharminfo.univie.ac.at

Gerhard F. Ecker is an Austrian medicinal chemist and expert in the fields of Pharmacoinformatics at the University of Vienna, where he is the Professor for Pharmacoinformatics and Head of the Pharmacoinformatics Research Group at the Department of Medicinal Chemistry. He also coordinates the research focus "Computational Life Sciences" of the Faculty of Life Sciences.

Contents

Career

Ecker received his doctorate in natural sciences from the University of Vienna in 1991, [2] became appointed Associate Professor for Medicinal Chemistry in 1998 and Full Professor for Pharmacoinformatics in 2009. [3]

Ecker is Editor of Molecular Informatics [4] and coordinates the EUROPIN PhD programme in Pharmacoinformatics.[ citation needed ] Currently he is also President of the European Federation for Medicinal Chemistry. [5]

Research

Ecker's research focuses on computational drug design which not only led to the identification of highly active propafenone-type inhibitors of P-glycoprotein, [6] [7] [8] but also paved the way for development of new descriptors and virtual screening approaches for identification of new scaffolds active at P-gp. With the increasing knowledge on the importance of P-gp for ADME, his interest moved towards the prediction of P-gp substrate properties. [9] Around 2010 he extended the studies also on other antitargets, such as the hERG potassium channel, [10] as well as on the serotonin transporter, [11] the GABA receptor [12] and the insulin receptor. [13]

Related Research Articles

<span class="mw-page-title-main">Drug design</span> Invention of new medications based on knowledge of a biological target

Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Drug design frequently but not necessarily relies on computer modeling techniques. This type of modeling is sometimes referred to as computer-aided drug design. Finally, drug design that relies on the knowledge of the three-dimensional structure of the biomolecular target is known as structure-based drug design. In addition to small molecules, biopharmaceuticals including peptides and especially therapeutic antibodies are an increasingly important class of drugs and computational methods for improving the affinity, selectivity, and stability of these protein-based therapeutics have also been developed.

<span class="mw-page-title-main">Ligand (biochemistry)</span> Substance that forms a complex with a biomolecule

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ligare, which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure.

Neuropeptide Y receptors are a family of receptors belonging to class A G-protein coupled receptors and they are activated by the closely related peptide hormones neuropeptide Y, peptide YY and pancreatic polypeptide. These receptors are involved in the control of a diverse set of behavioral processes including appetite, circadian rhythm, and anxiety.

<span class="mw-page-title-main">(+)-CPCA</span> Stimulant drug

(+)-CPCA is a stimulant drug similar in structure to pethidine and to RTI-31, but nocaine is lacking the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.

<span class="mw-page-title-main">Lobeline</span> Chemical compound

Lobeline is a piperidine alkaloid found in a variety of plants, particularly those in the genus Lobelia, including Indian tobacco, Devil's tobacco, great lobelia, Lobelia chinensis, and Hippobroma longiflora. In its pure form, it is a white amorphous powder which is freely soluble in water.

Muscarinic acetylcholine receptor M<sub>5</sub> Protein-coding gene in the species Homo sapiens

The human muscarinic acetylcholine receptor M5, encoded by the CHRM5 gene, is a member of the G protein-coupled receptor superfamily of integral membrane proteins. It is coupled to Gq protein. Binding of the endogenous ligand acetylcholine to the M5 receptor triggers a number of cellular responses such as adenylate cyclase inhibition, phosphoinositide degradation, and potassium channel modulation. Muscarinic receptors mediate many of the effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor have not been fully explored; however, stimulation of this receptor is known to effectively decrease cyclic AMP levels and downregulate the activity of protein kinase A (PKA).

Dopamine receptor D<sub>2</sub> Main receptor for most antipsychotic drugs

Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.

Adenosine A<sub>2B</sub> receptor Cell surface receptor found in humans

The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human adenosine A2b receptor gene which encodes it.

<span class="mw-page-title-main">GPR55</span> Protein-coding gene in the species Homo sapiens

G protein-coupled receptor 55 also known as GPR55 is a G protein-coupled receptor that in humans is encoded by the GPR55 gene.

Dopamine receptor D<sub>3</sub> Subtype of Dopamine Receptor

Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 2</span> Mammalian protein found in humans

Metabotropic glutamate receptor 2 (mGluR2) is a protein that, in humans, is encoded by the GRM2 gene. mGluR2 is a G protein-coupled receptor (GPCR) that couples with the Gi alpha subunit. The receptor functions as an autoreceptor for glutamate, that upon activation, inhibits the emptying of vesicular contents at the presynaptic terminal of glutamatergic neurons.

<span class="mw-page-title-main">Metabotropic glutamate receptor 3</span> Mammalian protein found in humans

Metabotropic glutamate receptor 3 (mGluR3) is an inhibitory Gi/G0-coupled G-protein coupled receptor (GPCR) generally localized to presynaptic sites of neurons in classical circuits. However, in higher cortical circuits in primates, mGluR3 are localized post-synaptically, where they strengthen rather than weaken synaptic connectivity. In humans, mGluR3 is encoded by the GRM3 gene. Deficits in mGluR3 signaling have been linked to impaired cognition in humans, and to increased risk of schizophrenia, consistent with their expanding role in cortical evolution.

5-HT<sub>7</sub> receptor Protein-coding gene in the species Homo sapiens

The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) The 5-HT7 receptor is coupled to Gs (stimulates the production of the intracellular signaling molecule cAMP) and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels. This receptor has been a drug development target for the treatment of several clinical disorders. The 5-HT7 receptor is encoded by the HTR7 gene, which in humans is transcribed into 3 different splice variants.

<span class="mw-page-title-main">GABA transporter type 1</span> Protein-coding gene in the species Homo sapiens

GABA transporter 1 (GAT1) also known as sodium- and chloride-dependent GABA transporter 1 is a protein that in humans is encoded by the SLC6A1 gene and belongs to the solute carrier 6 (SLC6) family of transporters. It mediates gamma-aminobutyric acid's translocation from the extracellular to intracellular spaces within brain tissue and the central nervous system as a whole.

<span class="mw-page-title-main">GHB receptor</span> GHB receptor coding gene in the species Homo sapiens

The γ-hydroxybutyrate (GHB) receptor (GHBR), originally identified as GPR172A, is an excitatory G protein-coupled receptor (GPCR) that binds the neurotransmitter and psychoactive drug γ-hydroxybutyric acid (GHB). As solute carrier family 52 member 2 (SLC52A2), it is also a transporter for riboflavin.

<span class="mw-page-title-main">Quipazine</span> Chemical compound

Quipazine is a serotonergic drug of the piperazine group which is used in scientific research. It was originally intended as an antidepressant but never developed for medical use.

The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor, is a type of nicotinic acetylcholine receptor, consisting of α3 and β4 subunits. It is located in the autonomic ganglia and adrenal medulla, where activation yields post- and/or presynaptic excitation, mainly by increased Na+ and K+ permeability.

<span class="mw-page-title-main">Naphthylpiperazine</span> Chemical compound

1-(1-Naphthyl)piperazine (1-NP) is a drug which is a phenylpiperazine derivative. It acts as a non-selective, mixed serotonergic agent, exerting partial agonism at the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F receptors, while antagonizing the 5-HT2A, 5-HT2B, and 5-HT2C receptors. It has also been shown to possess high affinity for the 5-HT3, 5-HT5A, 5-HT6, and 5-HT7 receptors, and may bind to 5-HT4 and the SERT as well. In animals it produces effects including hyperphagia, hyperactivity, and anxiolysis, of which are all likely mediated predominantly or fully by blockade of the 5-HT2C receptor.

<span class="mw-page-title-main">Clorotepine</span> Antipsychotic medication

Clorotepine, also known as octoclothepin or octoclothepine, is an antipsychotic of the tricyclic group which was derived from perathiepin in 1965 and marketed in the Czech Republic by Spofa in or around 1971 for the treatment of schizophrenic psychosis.

References

  1. Williams, A. J.; Harland, L.; Groth, P.; Pettifer, S.; Chichester, C.; Willighagen, E. L.; Evelo, C. T.; Blomberg, N.; Ecker, G.; Goble, C.; Mons, B. (2012). "Open PHACTS: Semantic interoperability for drug discovery" (PDF). Drug Discovery Today . 17 (21–22): 1188–1198. doi: 10.1016/j.drudis.2012.05.016 . PMID   22683805.
  2. His university-hosted CV - "Gerhard Ecker Home". Archived from the original on 2011-09-18. Retrieved 2011-12-07. - this cross-references with his publications on Google Scholar: https://scholar.google.com/scholar?as_q=&as_sauthors=Gerhard+Ecker+Fleischhacker+Noe
  3. Bio from wiley.com - for Transporters as Drug Carriers: Structure, Function, Substrates, Volume 44 - http://onlinelibrary.wiley.com/book/10.1002/9783527627424/homepage/AuthorBiography.html
  4. Molecular Informatics
  5. European Federation for Medicinal Chemistry
  6. Jabeen, I.; Wetwitayaklung, P.; Klepsch, F.; Parveen, Z.; Chiba, P.; Ecker, G. F. (2011). "Probing the stereoselectivity of P-glycoprotein—synthesis, biological activity and ligand docking studies of a set of enantiopure benzopyrano\3,4-b]\1,4]oxazines". Chemical Communications. 47 (9): 2586–2588. doi:10.1039/C0CC03075A. PMID   21173990. S2CID   205756984.
  7. Sugano, K.; Kansy, M.; Artursson, P.; Avdeef, A.; Bendels, S.; Di, L.; Ecker, G. F.; Faller, B.; Fischer, H.; Gerebtzoff, G. G.; Lennernaes, H.; Senner, F. (2010). "Coexistence of passive and carrier-mediated processes in drug transport". Nature Reviews Drug Discovery. 9 (8): 597–614. doi:10.1038/nrd3187. PMID   20671764. S2CID   34829942.
  8. Klepsch, F.; Ecker, G. F. (2010). "Impact of the Recent Mouse P-Glycoprotein Structure for Structure-Based Ligand Design". Molecular Informatics. 29 (4): 276–86. doi:10.1002/minf.201000017. PMC   6422301 . PMID   27463054.
  9. Parveen, Z.; Stockner, T.; Bentele, C.; Pferschy, S.; Kraupp, M.; Freissmuth, M.; Ecker, G. F.; Chiba, P. (2010). "Molecular Dissection of Dual Pseudosymmetric Solute Translocation Pathways in Human P-Glycoprotein". Molecular Pharmacology. 79 (3): 443–452. doi:10.1124/mol.110.067611. PMC   6422312 . PMID   21177413.
  10. Thai, K. M.; Windisch, A.; Stork, D.; Weinzinger, A.; Schiesaro, A.; Guy, R. H.; Timin, E. N.; Hering, S.; Ecker, G. F. (2010). "The hERG Potassium Channel and Drug Trapping: Insight from Docking Studies with Propafenone Derivatives". ChemMedChem. 5 (3): 436–442. doi:10.1002/cmdc.200900374. PMID   20146282. S2CID   23597808.
  11. Sarker, S.; Weissensteiner, R.; Steiner, I.; Sitte, H. H.; Ecker, G. F.; Freissmuth, M.; Sucic, S. (2010). "The High-Affinity Binding Site for Tricyclic Antidepressants Resides in the Outer Vestibule of the Serotonin Transporter". Molecular Pharmacology. 78 (6): 1026–1035. doi:10.1124/mol.110.067538. PMC   4513247 . PMID   20829432.
  12. Khom, S.; Strommer, B.; Ramharter, J.; Schwarz, T.; Schwarzer, C.; Erker, T.; Ecker, G. F.; Mulzer, J.; Hering, S. (2010). "Valerenic acid derivatives as novel subunit-selective GABAA receptor ligands -in vitro and in vivo characterization". British Journal of Pharmacology. 161 (1): 65–78. doi:10.1111/j.1476-5381.2010.00865.x. PMC   2962817 . PMID   20718740.
  13. Search Results for author Ecker GF on PubMed .