The best of 2019: an A–Z of drug discovery research

Catch up on 2019 on RxNet and in drug discovery, in our round-up of the highlights from the year – from A through to Z.

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Artificial intelligence

Artificial intelligence (AI) continues to be a growing area of exploration for many involved in drug discovery –being implemented at all stages of the pipeline. This year, we reported on how an AI collaboration led to the discovery that many existing drugs have the potential to treat age-related macular degeneration (AMD), as well as a novel deep learning tool that can be implemented to provide accurate models of a cell’s response to perturbations such as disease, the introduction of drug compound and genetic interventions.

For more, you can also check out our Ask the Experts on artificial intelligence

Biophysics

Biophysical imaging techniques, such as x-ray crystallography, NMR spectroscopy, cryo-electron microscopy (cryo-EM), have become a standard part of the drug discovery process for academic researchers and pharmaceutical companies. In our second spotlight of the year, we explored this field speaking to a range of experts about their research and highlighted relevant news including how Oregon based researchers used cryo-EM determine the three major structures of the anxiety and depression-associated serotonin transporter, which they believe could be used in the hunt for new addiction therapeutics.

Chicken egg

A study initially set out to use chickens to grow eggs that contained high-quality proteins for use in scientific research. As the investigation went on, the researchers realized that the method could also be used to produce proteins used in creating drugs, and is just as efficient as existing methods and potentially more cost effective. Their work could revolutionize drug development techniques, allowing the development of more economical protein-based drugs. 

Drug repurposing

Rather than focusing their research efforts on developing new molecular entities to treat diseases, some researchers are looking to previously developed drugs (some that gained approved, some that have not) to treat the disease they were not initially developed for. From a repurposing metformin to repair damaged brain cells to using a B-cell tumor drug as a potential new treatment for metabolic diseases, many researchers are definitely taking advantage of these well-known off-target side interactions drugs can have in the body.

You may also be interested in our In Focus on polypharmacology

Erdaftinib (BALVERSA™)

The first FGFR kinase inhibitor was approved by the US FDA in April. Results from a Phase II clinical trial, Janssen Pharmacueitcal’s (Beerse, Belgium) erdaftinin (sold under the name BALVERSA™) received accelerated approval. This comes after FDA breakthrough therapy designation in March 2019 and priority review designation of the NDA submitted in September 2018. This, once-daily oral FGFR kinase inhibitor is indicated for the treatment of certain adults with locally advanced or metastatic urothelial carcinoma (mUS). This approval brought a novel treatment option for a small subset of urothelial carcinoma patients who typically have limited treatment options. 

Future Drug Discovery

In March, our latest partner journal, Future Drug Discovery, was launched! This journal aims to cover the latest in drug discovery, research and development. March technically saw the first paper published online but the first issue was released this summer. We introduced this new journal to RxNet members with a two-part interview; the first discussed the new journal with the Managing Editor of the Journal, followed by a Peek behind the Paper interview, with the corresponding author of the first article.

Be sure to check out all the content from Future Drug Discovery here  

Glossary of drug discovery

In partnership with Future Drug Discovery, we created and published ‘The RxNet Glossary of Drug Discovery’. The editorial teams of RxNet and Future Drug Discovery worked closely together with leading experts from industry and academia to develop this comprehensive and holistic overview of this field – bridging the gap between established scientists and the general public.

Halichondrin

Halichondrin is a proven potent anti-cancer agent that, although found naturally in sea sponges, can only be acquired in tiny quantities. In a landmark development – researchers, for the first time, discovered a way to synthesize substantial quantities of E7130, a drug candidate from the halichondrin class. Synthesizing larger quantities of this compound will allow them to perform detailed studies on its biological activity, pharmacological properties and efficacy.

Inhalable mRNA

mRNA has the potential to treat a huge range of diseases, however, the safe and efficient delivery is often seen as an obstacle in its use. At the beginning of the year, we saw MIT (MA, USA) researchers design inhalable particles that can deliver mRNA directly into the lungs. This work overcomes the issues that hinder its widespread use as therapeutic and could lead to novel therapies for those with cystic fibrosis, of whom new treatments are desperately needed. 

JEUVEAU™

In February, the US FDA approved JENVEAU™, indicated to improve the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adults. This approval marks the first FDA approval for an aesthetic neurotoxin and makes Evolus (CA, USA) – who developed this compound – the first company to enter this market in almost 10 years.

Find all the US FDA approval from 2019 here

Kidney inflammation

In models of the diseases, a synthetic peptide was reported to promise in treating nephritis. The peptide directly disrupts destructive inflammation, a hallmark of the disease, allowing the kidneys to recover better and maintain their function. Could this peptide aid recovery from chronic kidney disease, something many patients experience if their kidneys are not completely destroyed by nephritis? 

Light-induced proton transfer

During drug screening, knowing whether an asymmetric molecule is ‘left-handed’ or ‘right-handed’ in is critical information for researchers. The ‘handed-ness’ can completely change the way a molecule behaves. The prevalence of children born with birth defects after their mothers took thalidomide in the 1950s, highlights how essential this information is for drug developers – the left-handed version of this molecule is toxic. This year, a Florida-based team developed a way to turn a left-handed molecule into a right-handed one – using light-induced proton transfer. 

Machine learning

The topic of artificial intelligence and machine learning has attracted a lot of attention over the past year on RxNet.  Here, a machine-learning algorithm that boasts an accuracy of 90% when predicting the outcome of chemical reactions has been created. Typically, trained human chemists only have an accuracy of 80%, hence this could help researchers reduce the time spent in preclinical work and allow for many to avoid the ‘trial-and-error’ nature of making molecules used today.

Non-opioid pain relief

There is a dire need for alternative and effective options for pain relief, which do not carry the same negative side effects as seen with opioids. In this work, an international team of researchers have demonstrated how utilizing nanoparticles to target delivery to NK1Rs in endosomes which are known to be responsible for producing signals to maintain pain. 

On-a-chip

Lab-on-a-chip, organ-on-a-chip… microfluidics and ‘-on-a-chip’-based technologies could be set to be the future of drug discovery. A microfluidic-based drug screening chip was developed by researchers from Korea, which allows for the comparison of critical pharmacological patterns – identifying synergistic interactions – between antibiotics. The device enables researchers to explore the combinatorial testing in the process of finding the antibiotic pairs that together work best against pathogens.

PROTACs

As a promising alternative to small molecule inhibitors, PROTACs – or Proteolysis Targeting Chimeras –  are an interesting area of research some are beginning to explore. Rather than rely on the binding of a classic inhibitor to the target protein for its effects to be seen, PROTACs can inhibit and degrade any target protein by simply recruiting E3 ligase protein complexes to the target and initiate degradation. See how this approach is being applied in neurology

Quality

Quality is key in drug discovery. New techniques are constantly being developed to help produce purer and safer drugs. In a world-first breakthrough, this team invented a novel method that could accelerate the discovery of new drugs – drugs of a higher quality. 

Rising drug prices

With just a quick look in the news you can find a plethora of articles, news and opinion pieces discussing drug pricing; ‘Why do prescription drugs cost so much?’, ‘How do companies decide drug prices?’, ‘The X million-dollar drug’ and the list goes on. Interestingly, a paper published earlier this year shed light a reason as to why drug prices are rising; it's not just new drugs entering the market but drug companies are also increasing the prices on lower drugs. 

Synthetic peptide

In this research, we learnt about how Aβ plaques may not be the main culprit behind Alzheimer’s disease – rather it is smaller oligomers that are the toxic agents. Leading on from this, the team then went on to describe how synthetic α-sheets can actually block this by binding to and neutralizing the toxic oligomers.

Thalidomide

After first being introduced onto the market as a morning sickness drug, thalidomide was then taken off the shelf due to its associated birth defects such as shortened limbs and defective organs. Now, more light has been shed on the mechanism behind the limb abnormalities caused by this notorious drug. Studies in zebrafish models identified cereblon as the primary target protein that mediates its teratogenic and antimyeloma activates. Further insight into thalidomide could result in the development of safer thalidomide-based drugs to treat a range of diseases. 

Underwater

For years, we have relied on the actinobacteria as the microbe of choice for deriving new antibiotics and medicines; this microbe accounts for half of the 20,00+ microbe derived drug candidates. However, we are now facing the issue of our limited supply running out. Combining this with the ever-looming issue of the fast emergence of antibiotic resistance, we need to start being more creative in where we find novel drugs. Fortunately, the marine Actinobacteria is relatively unexplored and may prove an even richer source of bioactive microbial molecules. 

Velcro-like protein

Cytokines have been recognized by many for their potential therapy for cancer; unfortunately, their low selectivity, high toxicity and ability to leak into the bloodstream has hindered their potential. In efforts to overcome this, MIT-based researchers developed a novel technique that prevents cytokine leakage, following their discovery of a ‘velcro-like’ protein (lumican) that attaches itself to both the therapeutic cytokine and tumor tissue. This protein could be applied to prolong cytokine action at the target site.

Women in drug discovery

As part of International Women’s Day (8 March 2019), we spoke with four female scientists involved in drug discovery. In this four-part series, they shared with us their experiences (both the good and not-so-good), their inspirations, what a 'day in a life' looks like for them, and the advice they have to pass onto the next generation of scientists and researchers. 

X-ray structure

Researchers have solved the x-ray structure of the enzyme that makes obafluorin – a broad-spectrum antibiotic agent. Importantly, the structure of obafluorin is completely different to all FDA-approved antibiotics. Despite this being the first step in the long drug-development process, we are in dire need of a class of antibiotics that have not been contaminated by clinical resistance. This work could lead to the next generation of antibiotics for humans.

Young scientists

In 2020, we’re looking to expand the opportunities on the site for those at the beginning of their careers in drug discovery and we are looking to recruit members to join Early Career Panel. This position is open to those within the first 6 years of their first academic or industrial appointment and would involve responsibilities such as promoting the site, directing the content, both in the form of writing articles for the site and giving advice as to topics to cover or focus on.

Find out more here

ZULRESSO™

In March, we saw the US FDA approve ZULRESSO™, the first and only treatment specifically indicated to treat postpartum depression – a common medical complication of childbirth that affects approximately one in nine women in the US. Postpartum depression can have significant and long-term impacts on both the woman and their family, which makes this a big step in the advancement of drugs for women’s mental health. 


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