I guarantee that no one wants to hear about this. Heck, I don't, either, but I'm going to write about it anyway. That's because while most of the world has been enjoying a respite from the coronavirus (at least compared to the 2020-2022 situation), it doesn't mean that this is always going to be the case. In a couple of months, we're going to be undeniably in the Fall season in the northern hemisphere. Schools at all levels will be opening up soon, and as we keep going into the latter part of the year we will inexorably be spending less time out in the open air and more time in smaller rooms w ..read more

I've written several times here about the association between bacteria species and various types of cancer (most recent post). There seems little doubt that there is such an association, although what it means and what we can learn from it, those are the hard parts. There was a paper in 2020 that suggested that working out the bacterial species involved could be used as a diagnostic approach, which is one of the things that could be quite useful. That's especially so since the authors reported using plasma samples for these diagnoses, looking for pieces of microbial DNA and working from there ..read more

Word came over the weekend that Albert Eschenmoser had died at just a few weeks short of his 98th birthday (!) The late-20th-century giants of organic chemistry continue to leave us one by one. Eschenmoser will forever be identified with the ETH in Zürich (undergraduate degree, then graduate work and afterwards joining the faculty. After becoming Professor Emeritus there in 1992 he took an appointment at Scripps as well, but maintained a lab at the ETH as well until retiring completely in 2009. During the 1960s he and his group was a key part of the landmark synthesis of vitamin B12, in a clos ..read more

As someone who worked in metabolic disease for some years earlier in my career, it's really hard to get across just how startling the GLP-1 drugs are for weight loss. I was quite struck by the early results (this 2021 blog post), and these have certainly been validated out in the broad patient population. The reason it's so strange to me is that there were decades of ideas that simply didn't work out - leptin, ghrelin, NPY5, CB1, and on and on. The whole field of pharmacological weight loss was a graveyard of ideas, a big sinkhole that people would back their money trucks up to and unload torr ..read more

I've written many times here about targeted protein degradation, and there's a vast amount of money and effort being poured into the field. Briefly summarized, if it's not something you follow, we medicinal chemists have traditionally tried to shut down the function of some protein by blocking its active site with some small molecule. At times we can alter things by binding somewhere else on the protein, in an allosteric site that changes the target protein's conformation and thus its activity. But TPD is something else again: it's a way to make the entire target protein disappear from the cel ..read more

There’s a tangled story playing out in solid state chemistry and physics right now, and I’m afraid it’s going to take some real time and effort to untangle. I’m talking about high-temperature superconductors, and some readers (like me!) will be old enough to remember the way that field changed forever in 1987 with the unexpected discovery of new materials that worked at higher temperatures than anyone had ever seen before. But one key feature of that discovery should not be overlooked in the light of current events: the behavior of those materials was quickly reproduced in several laboratories ..read more

It’s a sad and well-known fact that many cancer treatments buy time, but do not eliminate the underlying disease. That’s been changing over the years - there are more curative treatments than there used to be, and even the ones that just postpone things often do a much better job of it. But consider what you’re fighting against in oncology: cancer, as I’m fond of pointing out, is not a single disease, but rather hundreds (thousands) of them with a common feature of poorly-restrained cell growth. There are a lot of cellular growth pathways that can go wrong and lead to this, and similarly there ..read more

Two new papers have come out that illustrate a tug-of-war that's been going on for many years in drug research. On the positive side, there's this set of recommendations for chemical probes in the covalent-warhead and protein-degrader spaces. The authors (all very capable and experienced drug discovery scientists, some of whom I've worked with in the past) make a lot of really sound points. For example, for the covalent compounds, they divide these into target-focused and compound-focused critera. The former includes cellular assays (with attention to kinact/Ki values, a discussion of which I ..read more

A lot of researchers studying lifespan believe that there is (at some level) a tradeoff between aging and risk of cancer. The idea is that if you live long enough, you are more or less guaranteed to come down with one sort of cancer or another - there have been so many cell divisions along the way that some of them may well have gone wrong in some way, and so much cellular environmental wear and tear laid in on top of those. Now, it has to be said that not all of these cancerous events will directly lead to mortality; the connection is not so simple. For instance, it’s believed that a number o ..read more

Here’s a new paper that ties up a few coronavirus mysteries. I realize that not everyone wants to think about or hear about the virus, especially since much of the world has been getting a break from it these last few months, but the more we know about this particular pathogen, coronaviruses as a group, and viral infections in general, the better off we are. All three of these fields of knowledge have advanced during the pandemic, although we have certainly paid dearly for what we’ve been able to learn. As the world knows, SARS-CoV-2 was found to enter cells through the ACE2 protein (with help ..read more