As the population continues to grow, so does the incidence of disease and chronic conditions. Furthermore, the issues of drug resistance and antimicrobial resistance are making the field of drug discovery a challenge. Because of this, it’s important to discuss and address the potential of new drug modalities. The recent 4th Molecules Medicinal Chemistry Symposium – Harnessing the Power of New Drug Modalities conference (MMCS 2024) allowed experts in the field to discuss and collaborate on new research in the area.

In this article, we discuss the importance of continuing the conversation on the discovery of new drugs.

Population increase linked to disease incidence increase

Cancer research predicts that there will be 28 million new cancer cases worldwide each year by 2040; This is an increase of 54.9% from 2020.

In 2020 globally, 55 million people were living with Dementia. Altzheimers Disease International predicts that this number will almost double every 20 years; It’s expected to reach 78 million in 2030 and 139 million in 2050.  The majority of this increase is expected in the global south, where treatments are not as readily available.

New therapeutic drug targets for cancer

A speaker at the recent conference MMCS 2024, Dr Giuseppe La Regina, presented their research regarding establishing new targets for cancer therapies. Dr Giuseppe La Regina has previously investigated targets such as inhibitors of β caterin.

β caterin inhibitors

In a review published by Molecules Dr Giuseppe alongside other researchers investigated the prospects and current research surrounding inhibitors of β caterin.

β caterin is an important protein in cell development. It is a transcription factor responsible for the regulation of the Wnt gene, which has a range of roles regarding cell fate, proliferation, migration and cell death. However, accumulation of β caterin due to dysregulation of the Wnt/ β caterin pathway has been linked to various forms of cancer, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer.

Direct targeting of β caterin inhibitors can result in the downregulation of β caterin in certain cancers. Preventing the further accumulation of β caterin and its oncogenenic effects.

The researchers conclude that huge efforts are being made to discover direct inhibitors of β caterin as an anticancer therapy. However, there are a lot of factors which are affecting its progression. They suggest that further research is needed in the area of structural information of β caterin. As well as knowledge about the Wnt pathway and the cross-talk mechanisms involved in normal and pathological conditions.

Treatment for amyloid related diseases.

Another speaker who attended the MMCS 2024 was Professor Dr Carles Galdeano, who was invited to present his research regarding new drug targets for cancer therapy. However, he has also completed a lot of research in the field of amyloid-related diseases such as Alzheimer’s.

Proximity-induced pharmacology

Recently, alongside a team of researchers Professor Dr Carles Galdeano has published a review in Cells which outlines how proximity-induced pharmacology offers a new approach to treating amyloid-related diseases. The researchers explain that proximity-induced pharmacology can be used to target the underlying mechanism of disease progression by preventing the formation of amyloid plaques in the brain.

PIP uses compounds to hijack protein functions, often resulting in them being directed to and then interacting with other proteins which can result in the removal of the protein. PIP treatments can take various forms, including small-molecule drugs, peptides, antibody therapies, gene therapies, and chimeric molecules such as PROTACs (proteolysis-targeting chimeras), PhosTACs (phosphorylation-targeting chimeras), AUTACs (autophagy-targeting chimeras), among others.

autophagy-targeting chimeras utilise the autophagy pathway. This is a specialised pathway which can selectively degrade disease-causing proteins. It plays a vital role in maintaining cellular homeostasis, including clearing damaged and misfolded proteins. This is a key hallmark of amyloid-related diseases such as Alzheimer’s and Parkinsons’. Furthermore, these types of diseases often have mutations that affect this mechanism.

AUTACS have been specifically designed to selectively target and degrade abnormal proteins such as tau and α-syn implicated with the development of these diseases.The review goes on to conclude that there are a range of promising PIP treatments that could be used in the future for the treatment of amyloid-related diseases, as there is currently a lack of treatments within this area.

Population increase linked to drug resistance

As the population of the planet grows and certain diseases become more prevalent, so does drug resistance. Drug resistance is increasing due to increased treatment of certain diseases. This is becoming a common occurrence in HIV, caused by changes in the genetic structure of the disease. These changes affect the ability of the drugs to block the replication of the virus.  Drug resistance is also a huge problem in antibiotics due to antimicrobial resistance (AMR).

Antimicrobial resistance (AMR)

AMR is a big threat to public health. It is caused by superbug bacteria that can mutate and become resistant to antibiotics. Furthermore, they can pass their resistance genes to other bacterial species.

The World Health Organisation (WHO) estimate that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths. In addition, The United Nations estimates that by 2050 up to 10 million deaths could be caused by superbugs and AMR.

Antimicrobial resistance is fueled by their overuse in various industries including healthcare, agriculture and the pharmaceutical industries. Moreover, climate change and pollution are also facilitating the spread of AMR.

Temperature increases seen globally are accelerating the evolution of bacteria. Another concern is that extreme weather events such as floods allow pathogens from different ecosystems to mix, spreading resistant bacteria species. Furthermore, untreated wastewater from pharmaceutical and healthcare settings can also exacerbate the spread of resistant bacteria. As it often contains chemicals and antibiotics creating an ideal growth medium for resistant bacteria.

Antimicrobial resistance was a big discussion point at MMCS 2024. There were a wide range of presentations concerning AMR and potential future solutions.

Therapeutic approaches in fighting antimicrobial drug resistance

Dr Roberta Listro presented her research in Novel Therapeutic Approaches in Fighting Antimicrobial Resistance: Targeting LsrK in Bacterial Quorum Sensing.  A large volume of Dr Roberta Listros’s research focuses on the discovery of novel antimicrobial agents.

In 2023 she published a research article in Molecules alongside other collaborators some who also presented at MMCS 2024.

This included Dr Valeria Cavalloro, Dr Daniela Rossi, Professor Pasquale Linciano and chair of the conference Professor Simona Collina.

The research article also focuses on targeting bacterial quorum sensing as well as interfering with biofilm formation an innovative strategy to tackle AMR.  80% of human infections are caused by biofilms.

When protected by a biofilm bacteria have a 1000-fold higher tolerance to antibiotics. Biofilms are formed when microorganisms irreversibly attach themselves to a surface and grow. They secrete extracellular polymers which strengthen the attachment and growth of this community.

Quorum Sensing is a communication tool that is used by bacteria in the biofilm to communicate and organise the biofilm. Disrupting this communication would interfere with the formation of the biofilm and prevent further AMR from spreading.

The researchers targeted LsrK a bacterial kinase that is responsible for triggering quorum sensing. They tested the ability of three compounds to bind to the LsRK ligand, using fluorescence microscopy. They identified that one compound was more effective than the others at reducing biofilm formation.

Summary

MMCS 2024 covered a wide variety of topics in the area of drug discovery.  As the planet continues to evolve and become more populated it’s important to continue these discussions and to inspire new innovative solutions. As well as, to inspire the next generation of scientists and researchers.

If you missed MMCS 2024 but are interested in attending other conferences Molecules have a wide range of conferences throughout the year. If you’re interested in attending, see their page for more information.

Or if you’re interested in reading about other innovative therapies, see our recent post on Exploring the Science Behind Lion Mane Mushrooms.