Pharmacology Research Developments

Researchers at Johns Hopkins University have created a revolutionary protein “switch” that tricks cancer cells into manufacturing their own chemotherapy drugs, causing them to self-destruct while sparing healthy cells. Instead of delivering drugs directly to cancer cells, this method uses a harmless “prodrug” that only becomes activated inside cancer cells when the switch detects specific cancer markers. The switch is made by combining two proteins: one that senses cancer markers and another from yeast that converts the inactive prodrug into a potent cancer-killing drug. When the switch detects cancer, it activates the drug inside that cell, turning the cancer cell into a drug factory that destroys itself. To work, the switch must enter cancer cells either by delivering the protein itself or by inserting the gene that makes the protein, allowing the cancer cell’s own machinery to produce the switch. Afterward, patients receive the inactive chemotherapy prodrug, which becomes activated only inside cancer cells. This new approach focuses on producing the drug inside cancer cells rather than just delivering it to them, which could kill more cancer cells while reducing harmful side effects on healthy tissue. Lab tests on human colon and breast cancer cells have shown promise, and animal testing is expected to start within a year. While still early, this technique offers a radically different way to attack cancer. #PNAS #RMScienceTechInvest

The human microbiome is a distributed drug factory. A 2025 review in Natural Product Reports catalogued specialized metabolites, mapped by body site, with defined mechanisms. Gut: Cross-feeding between B. thetaiotaomicron, E. coli, and C. sporogenes redirects tryptophan flux toward indole-3-lactic acid (ILA) and indole-3-propionic acid (IPA), metabolites with anti-inflammatory and barrier-protective properties. Microbial catabolism of dietary fiber generates nicotinic acid that enters host NAD+ biosynthesis via the Preiss-Handler pathway. Skin: Commensal Staphylococcus produce peptides AIP-I and AIP-II, which disrupt MRSA quorum sensing, and Sh-lantibiotics α and β, ribosomally synthesized antimicrobial peptides that directly inhibit MRSA growth. Vaginal tract: L. gasseri expresses a biosynthetic gene cluster (BGC) encoding lactocillin, a thiopeptide with antimicrobial activity against Gram-positive bacteria. Respiratory tract: S. epidermidis produces epifadin, a compound with antimicrobial effects against methicillin-resistant S. aureus (MRSA). The pattern across all of these is commensal bacteria producing pharmacologically active compounds, in situ, under ecological pressure. BGC mining allowed for these discoveries, but the question of what's expressed, in which ecological contexts, and at what concentrations is still unresolved. That's what we hope to uncover next. Reference: Kulkarni et al. Mass spectrometry-based metabolomics approaches to interrogate host-microbiome interactions in mammalian systems. Nat Prod Rep. (2025). doi: 10.1039/d5np00021a.

Immune-boosting bacterial platform could aid nasal vaccines Outer membrane vesicles (OMVs) are non-living spherical #nanostructures that derive from the cell envelope of Gram-negative #bacteria. OMVs are important in bacterial #pathogenesis, cell-to-cell communication, horizontal #gene transfer, quorum sensing, and in maintaining bacterial fitness. These structures can be modified to express #antigens of interest using glycoengineering and genetic or chemical modification. The resulting #OMVs can be used to immunize individuals against the expressed homo- or heterologous antigens. Additionally, cargo can be loaded into OMVs and they could be used as a #drugdelivery system. OMVs are inherently #immunogenic due to proteins and glycans found on Gram negative bacterial outer #membranes. OMVs—non-infectious particles naturally released by some bacteria that are known to boost immunity—can enhance intranasal vaccines, strengthening levels of #protection at the point of #pathogen entry so those #vaccinated not only avoid getting sick but also avoid passing on the #infection to others. Abera Bioscience AB’s preclinical studies have shown their OMV-based platform triggers strong #immune responses against various bacterial and viral pathogens, inducing #mucosal immunity. Bacterial OMVs is being investigated for boosting mucosal immunity—which is believed could be key to stopping the onward transmission of several #viruses. Abera Bioscience researchers are modifying OMVs, developed on their proprietary vaccine platform, BERA, with antigens produced by cell-free-production methods, resulting in new immune-boosted nasal #vaccine sprays and powders. OMVs can be stockpiled and, in the event of a new pathogen threat, could be quickly coupled with different antigens to accelerate the #development of new vaccines. The plug-and-play #innovation also supports accessible pricing, facilitates #technology transfer, and has a favourable thermostability profile, all of which are beneficial qualities for LMICs. References: [1] https://lnkd.in/ghi38Bjt; [2] https://lnkd.in/gEtYjVB9 [3] https://lnkd.in/gHwaWbEV; [4] https://lnkd.in/gKsBXTg5 [5] https://lnkd.in/g-4xRS92; [6] https://lnkd.in/gKmJQUyY

🚀 The ADC Revolution: How "Biological Missiles" Are Transforming Cancer Antibody-drug conjugates (ADCs) are the precision-guided missiles of oncology—combining monoclonal antibodies, ultra-potent cytotoxic payloads, and smart linkers to deliver targeted destruction to cancer cells. With 15 FDA-approved ADCs and over 1,172 in development, this space is exploding—but what’s next? 🔥 Key Breakthroughs Changing the Game ➡️Breast Cancer: Enhertu (T-DXd) just secured FDA approval in 2025 after showing a 57.3% response rate (vs. 31.2% for chemo) in HER2-low metastatic breast cancer. ➡️Lung Cancer: T-DXd also shines in HER2-mutant NSCLC (38% response rate), while TROP2-targeted ADCs (like Datroway) extend survival in tough-to-treat cases. ➡️Dual-Payload ADCs: The next frontier—KH815 (TROP2 + dual payload) just entered Phase I, and 15+ others are in the pipeline, tackling resistance with two drugs in one. ⚙️ Tech Disruptions Driving Value ➡️Site-Specific Conjugation (e.g., Synaffix’s GlycoConnect™) is reducing toxicity—J&J and Boehringer just bet $1.3B on it. ➡️Beyond Chemo Payloads: STING agonists (Mersana Therapeutics), PROTAC degrades (DAC-Cullgen Inc.), and RNA disruptors (Heidelberg Pharma AG) are expanding ADC potential. ➡️Bispecific & Radioligand Hybrids: Imagine an ADC that also delivers radiation (Bayer/PeptiDream’s Ac-225 ADCs). 💡 Challenges = Investment Opportunities ❗️Manufacturing bottlenecks (auristatin shortages, 30-50% higher costs than mAbs). ❗️Toxicity management (interstitial lung disease, ocular effects). ❗️Regulatory hurdles (novel payloads add 12-18 months to the development process). 🌍 Beyond Oncology? ADCs are branching into autoimmune diseases ( Duality Biologics), chronic infections, and even brain disorders with BBB-penetrating designs (ABL Bio Inc. - ABL001). 💬 Let’s Discuss! Which ADC innovation excites you most—dual payloads, bispecifics, or non-chemo warheads? Can ADCs overcome manufacturing challenges to become first-line therapies? Which non-cancer application could be the next big market for ADCs? #biotechnology #investment #investor #drug #drugdevelopment #market #science #pharma #business #Biotech #VentureCapital #Investing #BusinessDevelopment #BD #investor _______________________________________________________________________________ 🔔 Follow for insights ♻️ Share to expand the network.

What if the next vaccine was designed before the outbreak began? Last time, we saw a “vaccine in a ball you could carry in your backpack.” That was about storage and portability. Here’s part two of the story: What if vaccines could be designed in weeks, not years? The Problem Today mRNA vaccines are powerful but fragile. To protect them, we wrap RNA inside tiny fat bubbles called lipid nanoparticles (LNPs). Here’s the bottleneck: there are thousands of possible bubble recipes. Each behaves differently in the body. Testing them one by one is slow, expensive, and unpredictable. The Breakthrough MIT researchers built an AI model trained on thousands of past LNP experiments. It learned the underlying patterns: which chemical structures, charges, and sizes made RNA delivery successful. Now, instead of trial-and-error, the AI can predict which new formulations will work best even with entirely new materials. And it’s not just theory: results published in Nature Nanotechnology showed these AI-designed particles worked in both lab cells and live models. Why This Matters Speed → Vaccine design shrinks from months to weeks. Precision → Tailored therapies for specific tissues, viruses, and even chronic diseases. Scale → Less wasted effort, lower costs, more access worldwide. The Bigger Picture If part one (the backpack nanoball) solved storage, part two (AI-driven design) solves speed. Together, they point to a future where vaccines and RNA therapies aren’t just reactive, they’re proactive. Suchitaa Paatil Sanju S Anju Goel Ajay Nandgaonkar Amit Saxena Taruna Anand #AI #HealthcareInnovation #Vaccines #RNA #mRNA #Biotech #FutureOfHealth #ArtificialIntelligence #DrugDiscovery #Innovation

I mentioned in my last post that we're previewing some of the more surprising findings from our upcoming CAM book. This is one of them. Silexan is a patented extract of lavender. It's been approved as a medication in 20 countries since 2009. In a head-to-head trial of 509 patients, it outperformed paroxetine for generalized anxiety disorder. Its effect size is 0.9. Compare that to antidepressants at 0.3 and benzodiazepines at 0.5. And it works through real pharmacology — modulating calcium signaling and glutamate release (similar to pregabalin), increasing extracellular serotonin (similar to SSRIs), and raising BDNF. No weight gain. No sedation. No sexual dysfunction. No tolerance or withdrawal. Seven large randomized trials. Regulatory approval across Europe. So why don't most American clinicians know about it? Because no one can patent lavender. And in the US, the financial incentives for FDA approval — application fees in the millions, trials in the billions — don't exist for natural compounds that can't be owned. In the US, Silexan is available over the counter as CalmAid — about $13 a month. In Europe, it's a regulated medication. Same compound. Same evidence. Different regulatory category depending on which side of the Atlantic you're on. Here's the other problem. Try telling a patient their anxiety treatment is "lavender" and watch their face. In the book, Chris Aiken, MD suggests introducing it to patients this way. Save the word "lavender" for last: → "There's a German medication called Silexan that works through serotonin and glutamate — with stronger anti-anxiety effects than most American medications." → "It's well tolerated. The most common side effect is lavender-flavored burps — because the medication was derived from the lavender plant." By the time you say "lavender," the patient has already heard the pharmacology. The name becomes a curiosity, not a credibility problem. We don't call bupropion an herbal treatment. It came from the African khat plant. Valproate was synthesized from valerian. The name shouldn't determine the credibility. The data should. One more preview coming soon — a cheat sheet of CAM options for the conditions that are hardest to treat with medications alone. ========== ❓ Have you tried Silexan with patients? What was their reaction when you told them it was derived from lavender? 🔄 If you know a colleague still searching for a benzo alternative, this one's worth sharing. 👍 Follow Daniel Carlat for more evidence-based psychiatry updates.

🚨 An HIV vaccine just passed a major clinical trial in humans! Over 80% of participants developed antibodies. In a major step forward in the search for an HIV vaccine, researchers have shown that an mRNA-based vaccine can successfully trigger the immune system to produce potent antibodies against HIV in humans. In a phase 1 trial, 80% of participants who received a version of the vaccine with a membrane-bound HIV envelope protein developed “tier 2” neutralizing antibodies—considered a significant benchmark in HIV vaccine development. These vaccines are modeled after the mRNA technology used in COVID-19 shots but are designed to display the virus’s surface proteins in a more realistic way, potentially guiding the immune system to attack the right viral targets. The study also found that this approach trained the body to make memory B cells and helper T cells, setting the stage for longer-lasting immunity. However, the study revealed an unexpected side effect: 6.5% of participants developed chronic hives, prompting long-term follow-up. Despite this, the results are promising enough to push this new vaccine platform into further trials aimed at generating broader protection. Unlike previous attempts that mostly failed to produce protective antibodies, this strategy targets hard-to-reach regions of the virus that are more likely to block infection. The findings could speed up HIV vaccine development, which has long struggled due to the virus’s high mutation rate and elusive nature. Researchers say the mRNA platform's speed and flexibility may finally offer a viable way forward in the decades-long effort to end the HIV epidemic. Parks, K. R., Moodie, Z., Allen, M. A., Yen, C., Furch, B. D., MacPhee, K. J., et al. (2025). Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial. Science Translational Medicine, 17(809).

🔬 Advancing ADME Profiling for PROTACs: New Insights Understanding the ADME behavior of PROTACs is critical as more molecules from this class advance into clinical development. This recent publication provides important insights into how conventional ADME assays perform when applied to PROTACs, a rapidly evolving therapeutic modality. Key findings include: 🔬 Conventional ADME assays (permeability, plasma protein binding) are limited for highly lipophilic PROTACs, with reliable results generally observed when ChromLogD is below 3.5–4. 🔬 Metabolic clearance (CLint) and blood-to-plasma (B:P) ratios are measurable across a wide range of lipophilicity, demonstrating robustness of these assays for PROTACs. 🔬 Implementation of an acetonitrile (ACN) wash step in Caco-2 permeability assays improved the detection of nonspecifically bound compounds. 🔬 Biorelevant solubility studies (using SGF, FaSSIF, FeSSIF) highlight the importance of gastrointestinal conditions in influencing solubility and absorption potential. These findings provide practical guidance for optimizing assay strategies and inform better decision-making during the discovery and development of PROTACs. This work is a significant step toward refining drug discovery processes for bRo5 molecules and addressing the unique challenges presented by PROTACs. Link: https://lnkd.in/gZZGvvgM #DrugDiscovery #DMPK #PROTACs #Pharmacokinetics #MedicinalChemistry #PharmaceuticalResearch

Today in Science Magazine, we report the late-stage functionalization of complex pharmaceutical scaffolds with bicyclobutane (BCB) strain-release warheads that enables a tunable approach to covalent inhibition. Several new bench stable, diversifiable S(IV) BCB-containing reagents have been developed with mild conditions to append them onto highly functionalized alkyl and (hetero)aryl amines, all of which are derived from (pre)clinical covalent inhibitors. The warheads are cysteine-selective, and their reactivity is highly tunable; the BCB sulfonamide, sulfonimidamide, and urea derivatives can be substituted in numerous ways to deliver a wide range of half-lives while maintaining selectivity. A co-crystal structure of a BCB-containing afatinib analog confirms covalent bond formation along with an array of biochemical studies. A head-to-head comparison of dacomitinib with its BCB analog showed a remarkable increase in selectivity in both the proteome and kinome, improved oral bioavailability and PK properties, and equivalent efficacy in an in vivo CDX model. The project was led by Zachary Shultz with significant contributions from Yun-Pu Chang. Earlier critical contributions to the project were made by Alessio Gabellini, PhD, Kyle Pedretty, and Thomas Scattolin. This manuscript is the culmination of several years of hard work and we are immensely grateful to our collaborators: Derek Duckett and Ansar Lee-Sam for the biochemical and in vivo work, Andrii Monastyrskyi and the Cancer PK/PD Core for ADME and PK studies, Ernst Schonbrunn, Luxin Sun, and the Chemical Biology Core for protein crystallography, John Koomen and the Proteomics and Metabolomics Core for proteomics support, and Lukasz Wojtas at USF for small molecule crystallography. https://lnkd.in/ej9V7xW7

Scientists may have found the key to defeating antibiotic-resistant superbugs. Researchers at the University of Kent and University College London have revealed that madecassic acid—a staple ingredient in K-beauty derived from the Centella asiatica herb—possesses powerful antibacterial properties. Traditionally used for its skin-calming effects, this plant-derived compound was found to effectively halt the growth of antibiotic-resistant E. coli. Through a combination of computer modeling and laboratory testing, the team demonstrated that the compound could even be modified into more potent versions, creating a versatile new template for drug development in the fight against increasingly resilient pathogens. What makes this discovery particularly promising is the compound's precision: it targets a specific protein system called the cytochrome bd complex, which bacteria need to breathe and survive but is completely absent in humans. This allows it to neutralize dangerous microbes without interfering with human biology, minimizing potential side effects. As global health experts warn that antimicrobial resistance could lead to 39 million deaths by 2050, these natural plant chemicals provide a critical lifeline, offering a faster and more sustainable path to discovering life-saving medicines than traditional synthetic drug development. source: University of Kent. (2026). Skincare Ingredient Fights Superbugs: Scientists discover skincare compound that kills drug-resistant bacteria. RSC Medicinal Chemistry.