What is it about?

The Multi-Targeting Drug DREAM Challenge was an effort to change drug development by challenging the scientific community to develop multi-targeting drugs for complex diseases. Traditionally, drug development has focused on precision medicine, where drugs are designed to target single molecules involved in a particular disease. However, this approach has its limitations, as many diseases are multifactorial and involve multiple interconnected pathways. That is, diseases are often changes in the body’s networks. As a result, targeting a single molecule may not be enough to produce a therapeutic effect. To address this challenge, the Multi-Targeting Drug DREAM Challenge invited the computational chemistry community to predict multi-targeting ‘network-based’ lead compounds for two specific diseases: RET-driven medullary thyroid cancer and TAUopathy disease, an inherited Alzheimer’s-like neurodegenerative disease. Participants were asked to submit computational models that could predict compounds that inhibit multiple targets previously identified in fruit fly (Drosophila) models. The challenge comprised three stages, where we evaluated the submitted models and selected the best-performing models. The most promising molecules were synthesized and tested for binding our proposed targets. By leveraging the collective expertise of scientists from different fields and backgrounds, the challenge provided a platform for identifying new multi-targeting ‘polypharmacology’ drug candidates that are capable of bringing the disease networks back towards normal. The use of computational models to predict the efficacy of multi-targeting drugs is a promising approach in drug development that is being widely adopted. It allows researchers to screen large libraries of compounds and predict which ones are most likely to have a therapeutic effect, while minimizing the need for expensive and time-consuming experimental studies. The Multi-Targeting Drug DREAM Challenge challenged the community to expand this approach, leading to the identification of new drug candidates that could target multiple proteins simultaneously, potentially changing the way we treat complex diseases.

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Why is it important?

One of the key benefits of multi-targeting drugs is their potential to be more effective than single-targeting drugs. By simultaneously targeting multiple molecules or pathways involved in a disease, multi-targeting drugs have the potential to produce more significant therapeutic effects. They also have the potential to reduce drug resistance and can even exhibit fewer side effects than traditional precision medicine drugs. Drug companies rarely work to create multi-targeting drugs, in part due to the complexity of developing a multi-targeting drug that is effective and safe. The DREAM Challenge was part of a larger effort to address these difficulties.


I am a biologist who is well aware of the complexity of diseases as they sit in our body. One way to address this daunting complexity is through 'network-based' approaches, a key focus of my laboratory and collaborators. This work connects computational chemistry with basic biological disease studies. My goal is to use this synthesis to develop a new generation of drugs better tuned to the whole body problem presented by diseases such as cancer and neurodegeneration, two of our biggest health challenges.

Ross Cagan
University of Glasgow

Read the Original

This page is a summary of: Crowdsourced identification of multi-target kinase inhibitors for RET- and TAU- based disease: The Multi-Targeting Drug DREAM Challenge, PLoS Computational Biology, September 2021, PLOS,
DOI: 10.1371/journal.pcbi.1009302.
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