Revolution in drug discovery: KIT develops groundbreaking platform!

Revolution in drug discovery: KIT develops groundbreaking platform!

Researchers at the Karlsruhe Institute of Technology (KIT) have developed an innovative drug discovery platform that has the potential to significantly increase the speed and efficiency of drug development. This platform uses extremely miniaturized nanodroplets with a volume of only 200 nanoliters per drop. This allows up to 1,000 experiments to be carried out on a single chip, significantly optimizing research processes.

The new technology enables the synthesis, characterization and testing of substances on the same chip. The goal is to make drug research more accessible and conserve resources. Current procedures are often costly and time-consuming, making them typically the preserve of large pharmaceutical companies. Professor Pavel Levkin from KIT's IBCS emphasizes the urgency of new drugs against resistance, especially in cancer therapy.

Advances in drug development

With this platform, a direct-to-biology approach was developed that makes it possible to carry out biological tests without additional preparation. In initial experiments, various potential MEK inhibitors were synthesized and tested. Within seven days, the researchers managed to produce 325 compounds, 46 of which showed comparable effectiveness to the established active ingredient mirdametinib. The tests were carried out on the colon cancer cell line HT-29, with the characterizing molecules examined using the MALDI-MSI method.

The new platform is not only seen as a step forward for high-throughput drug discovery, it also shows promising possibilities for the faster identification of effective substances. All 325 products could be analyzed in triplicate (975 samples) directly on the chip. The results were published in the scientific journalApplied Chemistrypublished (DOI: 10.1002/anie.202507586), which underlines the relevance and scientific value of this development.

Use of MEK inhibitors in other diseases

An example of the use of MEK inhibitors is the active ingredient PD98059. This reversible MEK inhibitor is being studied as a potential treatment for neurochemical changes in the brain in heart failure. In a rat model simulating human heart failure, central administration of PD98059 was shown to inhibit the phosphorylation of ERK1/2 in the paraventricular nucleus of the hypothalamus, leading to a reduction in sympathetic excitation and thus preventing clinical deterioration.

The pharmacokinetics of PD98059 show that it can be detected in various body tissues but has a short elimination half-life in plasma of approximately 73 minutes. To increase effectiveness, a sustained-release formulation was developed. This uses PD98059-loaded PLGA microparticles, which show stable plasma levels up to two weeks after subcutaneous injection. This novel therapeutic intervention could therefore enable significant progress not only in heart failure, but also in other diseases in which activated MAPK signaling plays a role.

In summary, it can be said that the developments at KIT and the research on MEK inhibitors such as PD98059 represent significant steps towards making drug discovery more efficient and effective. The increasing knowledge about the role of MAPK and mTOR signaling pathways in various cancer diseases could lead to new treatment options in the future, especially through combination therapies, as is discussed in the context of multikinase-targeting compounds.