In the DFG-MATH+ excellence cluster, Dr. Marcus Weber's group of the Zuse Institute Berlin is working together with other partners on the development of strong painkillers that do not show the usual side effects of opioids (e.g. of fentanyl). This project is based on preliminary work that had already led to a publication in Science in 2017.
In 2019, experimental results with the opioid substances FF6, FF3 and NFEPP have been published in the journal Scientific Reports* in cooperation between the Charité Campus Benjamin-Franklin and the Zuse Institute Berlin, which confirm and substantiate our computer-based predictions on the important role of the acidity (pKa value) of opioids. In a Charité press release on this article, Prof. Christoph Stein said: "Compared to the standard opioid fentanyl, the results of the novel substance class speak for themselves. [...] The closer the pKa value of the binding molecule is to the acid value (pH) of the inflamed or injured tissue, the more selectively only opioid receptors at the site of pain generation itself are activated and the lower is the risk of addiction or of side effects".
*Del Vecchio G, Labuz D, Temp J, Seitz V, Kloner M, Negrete R, Rodriguez-Gaztelumendi A, Weber M, Machelska H, Stein C. pK(a) of opioid ligands as a discriminating factor for side effects. Sci Rep. 2019 Dec 18;9(1):19344. doi: 10.1038/s41598-019-55886-1.
Fig.: Which modification of strong painkillers reduces the side effects? The supercomputer calculated a possible solution.
