Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Experimental and computational investigation of affinity and selectivity factors in CYP2D6 and CYP3A4 mediated metabolism

04.10.2010
While computer simulations of how the body metabolises drugs save both time and money, the best results when developing new drugs come from combining such simulations with laboratory experiments, reveals a researcher from the University of Gothenburg.

“My research demonstrates the benefits of combining traditional laboratory experiments with computer-based calculation models to understand and explain how the body’s various enzymes interact with a drug when breaking it down,” says Britta Bonn from the University of Gothenburg’s Department of Chemistry. “It can really help when developing and designing molecules with the desired metabolic characteristics for a new drug.”

When developing new drugs, it is important to understand how they will be broken down in the body, and which products are formed during this process. This breakdown of foreign substances is known as metabolism, and can be viewed as the conversion of the drug to a non-toxic, water-soluble product that can easily leave the body, in urine for example.

Enzymes does the job

Drug metabolism is the work of catalysts known as enzymes, and generally takes place in the liver. If a drug is broken down too effectively, it may not have the desired effect, and toxic metabolic products may form. It is therefore important to study and understand how drugs are broken down.

Traditionally laboratory experiments have been used to study drug/enzyme interactions, for example in cell-based systems in test tubes (in vitro). Recent years have also brought major progress in computer-based models (in silico) and information on the enzymes’ 3D structures.

Combines in vitro and in silico

Britta Bonn has focused on two important enzymes from the CYP family, which are the most common drug-metabolising enzymes, both in vitro and in silico to understand how they interact with foreign substances.

“My studies aimed to find out things like how well a molecule binds to the enzymes, why a molecule binds better to one enzyme than another, and how quickly and where in the molecule metabolism occurs,” says Bonn. “If we know more, we can change the molecules to produce the characteristics we’re after for new drugs.”

The thesis Experimental and Computational Investigation of Affinity and Selectivity Factors in CYP2D6 and CYP3A4 Mediated Metabolism will be defended on 24 September 2010. The supervisors were professor Kristina Luthman, professor Collen Masimirembwa and Dr Ismael Zamora.

Download the thesis.: http://hdl.handle.net/2077/22586

For more information, please contact:
Britta Bonn,
Tel. +46 707 91 36 57
+46 707 91 36 57
kjelland@chem.gu.se
Bibliographic data:
Title: Exploration of Catalytic Properties of CYP2D6 and CYP3A4 Through Metabolic Studies of
Levorphanol and Levallorphan.
Authors: Exploration of Catalytic Properties of CYP2D6 and CYP3A4 Through Metabolic Studies of
Levorphanol and Levallorphan. Bonn B., Masimirembwa C.M., and Castagnoli N. Drug Metabolism
and Disposition 2010, 38; 187-199.
Bonn B., Masimirembwa C.M., and Castagnoli N.
Journal: Drug Metabolism and Disposition 2010, 38; 187-199.
Link: http://dmd.aspetjournals.org/content/38/1/187

Helena Aaberg | idw
Further information:
http://hdl.handle.net/2077/22586
http://dmd.aspetjournals.org/content/38/1/187

More articles from Studies and Analyses:

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

nachricht Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>