Quantitative Risk Assessment Tool for Drug Racemisation

A brand new approach to test the probability of a medication turning out to be a potentially dangerous form of itself if this enters your body continues to be produced by research team at Cardiff College.

Together with Liverpool John Moores College and AstraZeneca, they allow us an easy method of trawl through large databases of prescription drugs and measure the likely chance of a medication undergoing racemisation – a procedure where a drug flips right into a mirror picture of itself and becomes either inert or potentially harmful.

‘New tool can rapidly predict the speed of racemisation in almost any drug compound, indicating how safe and productive that drug could be if administered.’

It’s the very first time that the quantitative risk assessment tool with this process continues to be developed. Publishing their new findings within the journal Angewandte Chemie, they believe the brand new method may potentially result in a significant decrease in the financial risk connected with drug development by identifying at-risk drug candidates in early stages within the production process, eventually resulting in the efficient growth and development of safe medication.
Drug compounds frequently appear in whether right- or left-handed form, with forms getting the same chemical composition however a structure that’s a non-superimposable mirror picture of each other. These compounds, referred to as enantiomers, tend to be like our left and right hands – they have a similar structure that completely mirrors each other, but it’s impossible to perfectly fit one on the top from the other with palms facing up.

Drugs can contain both right- and left-hands versions of the compound, but frequently just one of the drug’s enantiomers accounts for the preferred physiologic effects, as the other enantiomer is less active, inactive, or can occasionally produce negative effects.

The thalidomide crisis

The favourite illustration of this is actually the sedative drug thalidomide, that was discovered through the German company Chemie Grünenthal and offered in many countries around the globe from 1957 until 1961. It had been withdrawn in the market if this was discovered to result in of birth defects. One enantiomer caused the desirable sedative effects, as the other, unavoidably present, enantiomer caused the birth defects.

Because the thalidomide crisis, drug developers have worked to produce drugs that contains just one enantiomer.

However, it is possible that the single enantiomer can quickly switch towards the mirror picture of itself if this enters your body, via a process referred to as racemisation. This modification is regarded as brought on by the drug’s interaction with fundamental compounds within the water in your body.

Study overview

Within their study, they setup experiments that they simulated caffeine conditions of the body and introduced numerous drugs somewhere, monitoring the speed where the various drugs went through racemisation. With such results, they could produce a simple mathematical model that may rapidly predict the speed of racemisation in almost any drug compound, subsequently indicating how safe and productive that drug could be if administered.

Lead author from the study Dr Niek Buurma, from Cardiff University’s School of Chemistry, stated: “Following a thalidomide disaster, researchers worldwide have focussed on making compounds enantioselectively – that’s that contains only one enantiomer.

“However, while compounds are routinely tested to be inherently stable under physiological conditions, very little thought continues to be given regarding preventing configurational instability in the design stage, using appropriate predictive models.”

“We feel this risk-assessment will have the ability to fabricate safer medication by enhancing the pharmaceutical industry to rapidly place medication which will fail during development and concentrate their efforts on compounds that are more inclined to work.”

Source: Eurekalert

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