Connect with us


News

Discovery of new drug targets through computer program

Published

on


News, Pharmaceuticals, Processing Technologies

An international team has used software to find new targets for future drugs. The scientists discovered several new coupling sites in one of the largest protein families, where active substances can be targeted. The research team reports their findings in the scientific journal Nature Communications.

They form the largest family of proteins that serve as drug targets: G protein-coupled receptors, or GPCRs for short, are involved in numerous life processes. These include inflammation, sensory processing and the action of hormones. This is also reflected in the importance of these proteins for medicine: nearly one-third of prescription drugs target GPCRs. “To block or stimulate the proteins, you need active ingredients that fit precisely into one of the proteins’ numerous binding pockets,” explains pharmaceutical chemist Professor Dr. Peter Kolb of Philipps University in Marburg, one of the lead authors of the paper.

These proteins serve to transmit signals from the outside of a cell to its interior, enabling the cell to respond to changes in its environment. To exert their effects, hormones and other endogenous messengers couple to the binding pockets of these proteins. One can suppress the effect of these messengers by occupying the binding pockets elsewhere.

“However, the coupling sites used so far are often very similar to each other,” Kolb elaborates; “that’s why drugs often have too little selective effect.” This increases the risk of side effects. For example, beta blockers are used to block such a protein in the heart, but if the same target is switched off in the lung tissue, this can trigger asthma attacks.

To find new binding sites, the research groups of Kolb and his Marburg pharmacy colleague Professor Dr. Moritz Bünemann joined forces, both of whom belong to the research consortium GLUE; GLUE stands for “GPCR Ligands for Underexplored Epitopes”. The consortium is looking into the question of how drugs can be tailored so that they precisely match their targets, i.e. bring about fewer unintended side effects. The state of Hesse is supporting the Central Hesse project from 2020 to 2023 with a total of 4.6 million euros through its “LOEWE” funding program.

“We did a computer-based search for alternative binding sites on 113 different GPCR proteins. In this way, we actually found several binding pockets that have not previously been drug targets”

– Janik B. Hedderich

Experimental studies on two of the binding pockets found complement the calculations. “We inserted mutations into these two pockets,” explains co-author Moritz Bünemann. “The results confirm that these protein segments have a crucial function for the activity of the GPCR proteins.”

News Operation & Maintenance Processing Technologies

Stabilization of plastic exhaust systems during implementation

Published

on

According to the exhaust specialist ATEC from Neu Wulmstorf, the Vario roof flange can be mounted on all roofs with high fitting accuracy. The selection is based on the roof pitch and the required nominal size. In addition, the flange is suitable for temperature classes T200 and T250 – and ATEC has had this certified with a general design approval.

The new product combines two components: first, the flange itself, which provides a stable connection between the roof elevation and the roof structure, and second, the optional seal, a self-adhesive vapor retarder. The company provides two versions: for roof pitches between 0° and 30°, and from 30° to 60°, each in eight nominal sizes between DN60/100 and DN250/315. It is also compatible with plastic and metal exhaust systems up to a nominal operating temperature of ≤ 250 °C.

The flange consists of a stainless steel clamp to which two retaining lugs/articulated brackets are welded at the factory. This is accompanied by a cover plate measuring 450 x 450 mm and 0.5 mm thick. With the help of malleable perforated strips, the exhaust pipe together with the Vario roof flange is screwed into place. This allows the Vario to be used flexibly both in new buildings and in existing properties.

 

Continue Reading

News Operation & Maintenance Processing Technologies

Modern user interface impresses international jury

Published

on

SIG’s new intuitive Human Machine Interface (HMI) “SIG CRUISER” has been awarded the prestigious iF DESIGN AWARD 2022 in Gold – one of the most important design awards in the world. This part of SIG’s next-generation filling technology enables customers to easily control their entire production process. The user interface is designed to make the operator’s job much easier, while reducing the need for training and prior experience.

The award has been presented annually since 1954 by the iF Industrie Forum Design for outstanding achievements in product design. The company impressed the 132-member jury, which is made up of independent design experts from around the world, and won the award in the “User Interface (UI)” category. Out of nearly 11,000 entries, SIG CRUISER was awarded gold as one of 73 outstanding design achievements.

The judges made the following statement, “With a user-centric approach and sound development methodology, SIG CRUISER provides consistency from the store floor to the top floor, ensuring quick response times and convenience for both the operator and the service team. The user interface is exceptionally simple and user-friendly in terms of operations, layout and graphics, allowing a single operator to control the entire line.”

Today’s competitive environment requires companies to increase production and margins and optimize available equipment. To get the most out of filling lines, it is critical to reduce the risk of downtime and to interconnect, automate and monitor lines for maximum efficiency. The new user interface makes it possible to control the entire filling line. It displays KPIs in an intuitive way.

“This prestigious global design award is the result of the good cooperation between SIG and our partner, HMI Project GmbH. We are very proud that SIG CRUISER stood out from thousands of submissions and convinced the 132-member jury to award an iF DESIGN AWARD in Gold.”

– Stefan Mergel, Senior Product Manager Equipment

Continue Reading

Ingredients & Auxiliary Materials News Pharmaceuticals Processing Technologies

Innovative insights into emergence and classification into subtypes

Published

on

One of the deadliest tumor types is pancreatic cancer . The disease is often only discovered in locally advanced or metastasized tumor stages, when surgical intervention comes too late. Researchers led by Dr. Ivonne Regel of LMU Klinikum in Munich have now gained important new insights into the causes of tumor development. They have also succeeded in defining different tumor subtypes based on differences in their metabolic programs. Funded by the Wilhelm Sander Foundation, they are thus making a significant contribution to early detection and to individualized medicine in order to improve the chances of recovery for pancreatic cancer patients.

Pancreatic ductal adenocarcinoma, also known as pancreatic cancer, is a relatively rare but particularly malignant disease. It represents the fourth leading cause of cancer-related deaths in the European Union, and only about 10 percent of patients survive the first five years after diagnosis. This is due to aggressive growth and late diagnosis of the tumor. Pancreatic cancer often manifests itself only after other organs have already been affected and metastases are present. To improve the chance of cure for pancreatic cancer patients, it is of great urgency to find new biomarkers for early detection. Another essential step is to identify tumor-specific signaling pathways that cause aggressive disease progression in order to identify new targets for therapeutic approaches.

TLR3/IRF3/IRF7 signaling pathway critical for pancreatic cancer development

Pancreatic cancer development is a dynamic process involving tissue damage and inflammatory response in the pancreas. When pancreatitis occurs, the organ has a self-healing mechanism. Normal pancreatic cells can divide to replace damaged tissue. Molecules released during inflammatory and tissue-damaging processes are recognized by cell receptors, relaying signals that promote cell survival and division.

However, in pancreatic cells, this can contribute to cell degeneration and promote the development of pancreatic cancer. Researchers led by Dr. Ivonne Regel were able to show for the first time that the signaling pathway plays an important role in inflammatory responses not only in immune cells, but is also active in pancreatic cells of precursor lesions and tumor cells. This activation of the signaling pathway has an important function in pancreatic cancer development. Genetically-altered mice lacking a functional signaling pathway are unable to develop pancreatic carcinomas (see Figure). Similarly, it was genetically knocked out in pancreatic tumor cells using CRISPR/Cas9 gene scissors. These genetically modified tumor cells exhibited significantly less aggressive behavior in cell culture experiments and also showed greatly reduced metastasis in animal models.

“For the first time, we were able to demonstrate that an active signaling pathway in pancreatic cells contributes to the development of pancreatic cancer and also supports the formation of metastases.”

– Ivonne Regel

Dr. Regel’s team has made another exciting discovery: In pancreatic tumor cells, the signaling pathway surprisingly does not regulate known target genes; instead, evidence was found for epigenetic modifications. These are regulatory modifications to DNA and packaging proteins (histones) that influence the activity of genes. Thus, the current research results indicate that activation of the signaling pathway in tumor cells leads to high levels of transcription of specific tumor-promoting genes.

These genes primarily regulate tumor cell metabolism. This is particularly important because metabolites of tumor cells can be found in the blood of patients and can be used as biomarkers. “My team and I have succeeded in identifying different subtypes of pancreatic cancer from the blood of cancer patients based on differences in their metabolic programs” said Dr. Regel. “In further studies, we now want to find out to what extent the development of pancreatic cancer subtypes is regulated by the signaling pathway.”

 

Continue Reading