Metal-based complexes with their unique chemical properties, including multiple oxidation states, radio-nuclear capabilities and various coordination geometries yield value as potential pharmaceuticals. Understanding the interactions between metals and biological systems will prove key for site-specific coordination of new metal-based lead compounds. This study merges the concepts of target coordination with fragment-based drug methodologies, supported by varying the anomalous scattering of rhenium along with infrared spectroscopy, and has identified rhenium metal sites bound covalently with two amino acid types within the model protein. A time-based series of lysozyme-rhenium-imidazole (HEWL-Re-Imi) crystals was analysed systematically over a span of 38 weeks. The main rhenium covalent coordination is observed at His15, Asp101 and Asp119. Weak (i.e. noncovalent) interactions are observed at other aspartic, asparagine, proline, tyrosine and tryptophan side chains. Detailed bond distance comparisons, including precision estimates, are reported, utilizing the diffraction precision index supplemented with small-molecule data from the Cambridge Structural Database. Key findings include changes in the protein structure induced at the rhenium metal binding site, not observed in similar metal-free structures. The binding sites are typically found along the solvent-channel-accessible protein surface. The three primary covalent metal binding sites are consistent throughout the time series, whereas binding to neighbouring amino acid residues changes through the time series. Co-crystallization was used, consistently yielding crystals four days after setup. After crystal formation, soaking of the compound into the crystal over 38 weeks is continued and explains these structural adjustments. It is the covalent bond stability at the three sites, their proximity to the solvent channel and the movement of residues to accommodate the metal that are important, and may prove useful for future radiopharmaceutical development including target modification.

Marijuanas active components are potentially effective in treating pain, nausea, the anorexia of AIDS wasting, and other symptoms, and should be tested rigorously in clinical trials.

Alfa Cytology has launched its leukemia research services, focusing on small molecule drug development.

Experts gather to explore the latest breakthroughs in psychedelic research at international conference

The 18th Annual Pain Therapeutics Summit, a premier event bringing together leading experts in pain research and therapeutics, will take place from October 28th, 2024 to October 29th, 2024 in Boston, Massachusetts.

Alfa Cytology has introduced its advanced drug development services for brain tumors.

Feb 20, 2025, 11am EST

The Tufts CSDD postgraduate course in clinical pharmacology, drug development, and regulation is the longest-running professional development program in the biopharma space. Now in its 52nd year, this unique annual course prepares both new and experienced drug developers, regulators, policy makers, clinical investigators, and academic researchers for success in the life sciences sector. Thousands of drug development professionals are alumni of this prestigious one-of-a-kind program. Top speakers from industry, academia, and the FDA share their expertise to create a highly stimulating and rewarding learning environment.

Location Details: Virtual event via Zoom
Open to Public: No
Primary Audience(s): Faculty, Postdoctoral Fellows, Staff, Students (Graduate)
Event Type: Conference/Panel Event/Symposium, Lecture/Presentation/Seminar/Talk
Subject: Career Development, Health/Wellness, Innovation, Medicine, Science
Event Sponsor Details: Tufts Center for the Study of Drug Development
Event Contact Name: Sarah Wrobel
Event Contact Email: sarah.wrobel@tufts.edu
RSVP Information: secure.touchnet.net…
More info: csdd.tufts.edu…

Feb 13, 2025, 11am EST

The Tufts CSDD postgraduate course in clinical pharmacology, drug development, and regulation is the longest-running professional development program in the biopharma space. Now in its 52nd year, this unique annual course prepares both new and experienced drug developers, regulators, policy makers, clinical investigators, and academic researchers for success in the life sciences sector. Thousands of drug development professionals are alumni of this prestigious one-of-a-kind program. Top speakers from industry, academia, and the FDA share their expertise to create a highly stimulating and rewarding learning environment.

Location Details: Virtual event via Zoom
Open to Public: No
Primary Audience(s): Faculty, Postdoctoral Fellows, Staff, Students (Graduate)
Event Type: Conference/Panel Event/Symposium, Lecture/Presentation/Seminar/Talk
Subject: Career Development, Health/Wellness, Innovation, Medicine, Science
Event Sponsor Details: Tufts Center for the Study of Drug Development
Event Contact Name: Sarah Wrobel
Event Contact Email: sarah.wrobel@tufts.edu
RSVP Information: secure.touchnet.net…
More info: csdd.tufts.edu…

Feb 6, 2025, 11am EST

The Tufts CSDD postgraduate course in clinical pharmacology, drug development, and regulation is the longest-running professional development program in the biopharma space. Now in its 52nd year, this unique annual course prepares both new and experienced drug developers, regulators, policy makers, clinical investigators, and academic researchers for success in the life sciences sector. Thousands of drug development professionals are alumni of this prestigious one-of-a-kind program. Top speakers from industry, academia, and the FDA share their expertise to create a highly stimulating and rewarding learning environment.

Location Details: Virtual event via Zoom
Open to Public: No
Primary Audience(s): Faculty, Postdoctoral Fellows, Staff, Students (Graduate)
Event Type: Conference/Panel Event/Symposium, Lecture/Presentation/Seminar/Talk
Subject: Career Development, Health/Wellness, Innovation, Medicine, Science
Event Sponsor Details: Tufts Center for the Study of Drug Development
Event Contact Name: Sarah Wrobel
Event Contact Email: sarah.wrobel@tufts.edu
RSVP Information: secure.touchnet.net…
More info: csdd.tufts.edu…

Jan 30, 2025, 11am EST

The Tufts CSDD postgraduate course in clinical pharmacology, drug development, and regulation is the longest-running professional development program in the biopharma space. Now in its 52nd year, this unique annual course prepares both new and experienced drug developers, regulators, policy makers, clinical investigators, and academic researchers for success in the life sciences sector. Thousands of drug development professionals are alumni of this prestigious one-of-a-kind program. Top speakers from industry, academia, and the FDA share their expertise to create a highly stimulating and rewarding learning environment.

Location Details: Virtual event via Zoom
Open to Public: No
Primary Audience(s): Faculty, Postdoctoral Fellows, Staff, Students (Graduate)
Event Type: Conference/Panel Event/Symposium, Lecture/Presentation/Seminar/Talk
Subject: Career Development, Health/Wellness, Innovation, Medicine, Science
Event Sponsor Details: Tufts Center for the Study of Drug Development
Event Contact Name: Sarah Wrobel
Event Contact Email: sarah.wrobel@tufts.edu
RSVP Information: secure.touchnet.net…
More info: csdd.tufts.edu…

Join our daily and weekly newsletters for the latest updates and exclusive content on industry-leading AI coverage. Learn More Google DeepMind has unexpectedly released the source code and model weights of AlphaFold 3 for academic use, marking a significant advance that could accelerate scientific…

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders.

Significance Statement

Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling holds promise for treating metabolic and inflammatory diseases.

This new 10-minute TEDMED talk is getting quite a bit of attention:


 (if embedded video does not work, try the TED site itself.)

In it, Roger Stein claims to have created an approach to advancing drugs through clinical trials that will "fundamentally change the way research for cancer and lots of other things gets done".

Because the costs of bringing a drug to market are so high, time from discovery to marketing is so long, and the chances of success of any individual drug are so grim, betting on any individual drug is foolish, according to Stein. Instead, risks for a large number of potential assets should be pooled, with the eventual winners paying for the losers.

To do this, Stein proposes what he calls a "megafund" - a large collection of assets (candidate therapies). Through some modeling and simulations, Stein suggests some of the qualities of an ideal megafund: it would need in the neighborhood of $3-15 billion to acquire and manage 80-150 drugs. A fund of this size and with these assets would be able to provide an equity yield of about 12%, which would be "right in the investment sweet spot of pension funds and 401(k) plans".

Here's what I find striking about those numbers: let's compare Stein's Megafund to everyone's favorite Megalosaurus, the old-fashioned Big Pharma dinosaur sometimes known as Pfizer:

	Megafund (Stein)	Megalosaurus (Pfizer)
Funding	$3-15 billion	$9 billion estimated 2013 R&D spend
Assets	80-150	81 (in pipeline, plus many more in preclinical)
Return on Equity	12% (estimated)	9.2% (last 10 years) to 13.2% (last 5)

Since Pfizer's a dinosaur, it can't possibly compete with the sleek, modern Megafund, right? Right?

These numbers look remarkably similar. Pfizer - and a number of its peers - are spending Megafund-sized budget each year to shepherd through a Megafund-sized number of compounds. (Note many of Pfizer's peers have substantially fewer drugs in their published pipelines, but they own many times more compounds - the pipeline is just the drugs what they've elected to file an IND on.)

What am I missing here? I understand that a fund is not a company, and there may be some benefits to decoupling asset management decisions from actual operations, but this won't be a tremendous gain, and would presumably be at least partially offset by increased transaction costs (Megafund has to source, contract, manage, and audit vendors to design and run all its trials, after all, and I don't know why I'd think it could do that any more cheaply than Big Pharma can). And having a giant drug pipeline's go/no go decisions made by "financial engineers" rather than pharma industry folks would seem like a scenario that's only really seen as an upgrade by the financial engineers themselves.
A tweet from V.S. Schulz pointed me to a post on Derek Lowe's In the Pipeline blog. which lead to a link to this paper by Stein and 2 others in Nature Biotechnology from a year and a half ago. The authors spend most of their time differentiating themselves from other structures in the technical, financial details rather than explaining why megafund would work better at finding new drugs. However, they definitely think this is qualitatively different from existing pharma companies, and offer a couple reasons. First,

[D]ebt financing can be structured to be more “patient” than private or public equity by specifying longer maturities; 10- to 20-year maturities are not atypical for corporate bonds. ... Such long horizons contrast sharply with the considerably shorter horizons of venture capitalists, and the even shorter quarterly earnings cycle and intra-daily price fluctuations faced by public companies.

I'm not sure where this line of though is coming from. Certainly all big pharma companies' plans extend decades into the future - there may be quarterly earnings reports to file, but that's a force exerted far more on sales and marketing teams than on drug development. The financing of pharmaceutical development is already extremely long term.

Even in the venture-backed world, Stein and team are wrong if they believe there is pervasive pressure to magically deliver drugs in record time. Investors and biotech management are both keenly aware of the tradeoffs between speed and regulatory success. Even this week's came-from-nowhere Cinderella story, Intercept Pharmaceuticals, was founded with venture money over a decade ago - these "longer maturities" are standard issue in biotech. We aren't making iPhone apps here, guys.

Second,

Although big pharma companies are central to the later stages of drug development and the marketing and distributing of approved drugs, they do not currently play as active a role at the riskier preclinical and early stages of development

Again, I'm unsure why this is supposed to be so. Of Pfizer's 81 pipeline compounds, 55 are in Phase 1 or 2 - a ratio that's pretty heavy on early, risky project, and that's not too different from industry as a whole. Pfizer does not publish data on the number of compounds it currently has undergoing preclinical testing, but there's no clear reason I can think of to assume it's a small number.

So, is Megafund truly a revolutionary idea, or is it basically a mathematical deck-chair-rearrangement for the "efficiencies of scale" behemoths we've already got?

[Image: the world's first known dino, Megalosaurus, via Wikipedia.]

Samit Hirawat discussed India’s growing significance as a site for clinical trials, innovations in drug development, and how technology is poised to help bring new products to market faster

Marijuanas active components are potentially effective in treating pain, nausea, the anorexia of AIDS wasting, and other symptoms, and should be tested rigorously in clinical trials.

With the emergence of sofobuvir, a new direct acting antiviral, treatment for Hepatitis C infection is currently undergoing it's greatest change since the discovery of the virus 25 years ago. However Gilead, who manufacture the treatment, are under fire for the cost of the druge - around $90 000 for a course of treatment. Victor Roy, doctoral...

Inhibition of BET protein bromodomains BD1 and BD2 produces unique phenotypes in disease models.

Scientists have successfully developed a new technique to reliably grow crystals of organic soluble molecules from nanoscale droplets, unlocking the potential of accelerated new drug development.

Scientists have successfully developed a new technique to reliably grow crystals of organic soluble molecules from nanoscale droplets, unlocking the potential of accelerated new drug development.

Today I had the chance for a panel conversation with Geeta Vemuri from Baxter Ventures and Ed Silverman from Pharmalot blog (Wall Street Journal) at the Midwest Healthcare Venture Forum. Our general topic was how we (an entrepreneur and a corporate venture capitalist) look at bringing drugs/devices to market. Here are a couple of takeaways from our

The DRDO is making special N-99 masks, besides personal protective gear for chemical, biological, radiation and nuclear-related activities, and working on software, including one that will track people under quarantine.

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Medicinal chemists focus on the main protease of SARS-CoV-2 to develop antiviral treatments for the virus causing COVID-19

Medicinal chemists focus on the main protease of SARS-CoV-2 to develop antiviral treatments for COVID-19