Are you catching today’s 1:45pm session at ISPOR - “I Have a Better QALY Than You: How to Make Sense of Alternatives to the QALY for Research and Policymaking"? Tell us how you think the debate went, we want to hear your thoughts. #HEOR #ISPOR #DrugPricing #BioPharma #ISPOR24
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I Have a Better QALY Than You: How to Make Sense of Alternatives to the QALY for Research and Policymaking This promises to be compelling debate at ISPOR with Dan Ollendorf moderating. Our co-founder and chief scientific officer Darius Lakdawalla will be joined by Melanie Whittington and Anirban Basu. Learn more about the panel here: https://lnkd.in/gSAA-HZA #HEOR #ISPOR #DrugPricing #BioPharma #ISPOR24
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Our first paper pick for 2024 describes the discovery of IRAK4 inhibitors which benefited from inclusion of two hydroxyl groups at two different positions in the structures of the two clinical compounds. Read more at https://lnkd.in/e2gGa2ja #medicinalchemistry #drugdesign #drugdiscovery
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The staggering depletion of antibiotic pool is a cause for concern worldwide. To combat one of the biggest threats to humankind in today's world, #antimicrobialresistance, we present in our most recent study published in Cell Press, CLOVIBACTIN! https://lnkd.in/ek2f5Y_v Here we present he unusual path to the #discovery of clovibactin along with it's unique and multi-targeting attack #mechanism leaving harmful bugs like #MRSA helpless. This study is a big effort from our team at Utrecht University comprising of Markus Weingarth Eefjan Breukink Alexandre Bonvin Marc Baldus Maik Derks RAJ Pandit & Francesca Lavore; with major contributions from the group from Northeastern University and The University of Bonn and the pharmaceutical company NovoBiotic Pharmaceuticals. Our collaborators from University of Groningen & University of Florence provided crucial information to complete the story of Clovibactin. All in all it is has been a exciting story to work on, and it points in the direction of better #antibiotics, which are very much needed for the #future!
An antibiotic from an uncultured bacterium binds to an immutable target
sciencedirect.com
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Catch a concise 15 min update (or three) on key topics for the Pharamceutical Industry #methodmodernisation #nitrosamines #oligonucleotide analysis Link below ! #waters
Pssstt.... In the madness of preparing for Easter did you miss our event? 😲Not to worry, Pharma Insights 2024 is now available to watch on demand! 🤩 What a perfect way to enjoy the last of the chocolate 🍫 left from the weekend, in front of this great series of updates from experts in the field🥚 Talks about #methodmodernisation , #AQbD , #ICHQ14, #AllianceIS from Andrea Gheduzzi followed by a great update on #regulations and analytical techniques concerning #GTIs and #Nitrosamines by Amy Bartlett and to finish; a fantastic overview of the latest developments for #oligonucleotide analsysis and #newmodalities by Jonathan Fox Stay in the know and join the fun! https://lnkd.in/eTnqAFgq
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Today in ChemRxiv we report the regioselective, diversifiable hydroamination of unactivated olefins with diazirines. Over 50 examples highlight a broad functional group tolerance along with 14 late-stage, protecting group-free aminations of terpenes. https://lnkd.in/dScwtcgQ Our old friend [1.1.1]propellane even makes an appearance! Applications include target- and diversity-oriented syntheses of neramexane, mecamylamine, quinocide, a muscarinic M1 receptor agonist (from Sosei Heptares), and a nucleic acid splicing modulator (from Remix Therapeutics). We also report the synthesis of a bis-15N version of our diazirine. This required some new chemistry to ensure that 15N-ammonia was the ONLY source of the isotopic label. Single and double 15N transfer is now enabled with no redesign of the synthetic route required. This work was brought to fruition by the hard work and perseverance of Qingyu Xing, Preeti Chandrachud, PhD (now at Illumina), and Khalilia Tillett (now at Vilya).
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Principal & Advanced Therapies Practice Lead, DeciBio Consulting; Investor, BioTools Fund; Founder / Director, Suono Bio
Another day another piece of oligo news... This time from Tiba Biotech, who received a BARDA contract to leverage its non-LNP delivery technology for an RNAi-based treatment for swine flu. We wrote about the limitations of LNPs extensively over the years. They saved the day during the pandemic, but also stunted critical R&D on better, novel delivery technologies. LNPs are blunt instrument with lots of potential toxicity concerns. A better delivery vehicle would dramatically enhance the field of precision medicine and nucleic acid therapeutics. I suspect as the pandemic is further in the rear-view, we'll begin seeing more public work around novel delivery vehicles. What do you think about LNPs? We've called them "lamentable nano payloads" in the past. Do you agree? https://lnkd.in/g-csFF_f #oligo #RNA #drugdevelopment #pharma
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Medicinal Chemistry - Project Leader; Technology Innovation & External Platforms presso Alfasigma - parla di #scienze #farmaci #farmaceutico #ricerca #innovazione #sociale
PRODRUG: A NOVEL BIORESPONSIVE SELF-IMMOLATIVE SPACER Prodrugs are a very important chapter of medicinal chemistry. Starting from an HDAC inhibitor (ST7612AA1; Giannini, G., et al. J. Med. Chem. 2014. DOI: 10.1021/jm5008209) we previously explored binding to antibodies in the formation of ADCs (Antibody Drug Conjugates; Taddei, M , Giannini, G., et al., Chem. Sci. 2018. DOI: 10.1039/c7sc05266a). A stimuli-sensitive linker is one of the indispensable components of prodrugs for cancer therapy as it covalently binds the drug and releases it upon external stimulation at the tumour site. Quinone methide elimination has been widely used as the key transformation to release drugs based on their nucleofugacity. The usual approach is to bind the drug to the linker as a carbamate and release it as a free amine after a self-immolative 1,6-elimination. Although this approach is very efficient, it is limited to amines (as carbamates), alcohols or phenols (as carbonates) or other acidic functional groups. This research explored the effectiveness of a self-immolative spacer capable of directly connecting and releasing not only thyoles (e.g., ST7612AA1) but also amines, phenols, sulfonamides and carboxamides after a reductive stimulus. The spacer is based on the structure of (5-nitro-2-pyrrolyl)methanol (NPYM-OH), which was used for the direct alkylation of the functional groups mentioned above. This spacer is metabolically stable and has three indispensable sites for bioconjugation: the bioresponsive trigger, the conjugated 1,6 self-immolative system and a third arm suitable for conjugation with a carrier or other modifiers. The NPYM scaffold was validated by latestage functionalisation of approved drugs such as celecoxib, colchicine, vorinostat or ciprofloxacin. A hypoxia-activated NPYM-based prodrug (HAP) derived from HDAC inhibitor ST7612AA1 was also produced, which was active in cancer cells under hypoxic conditions. #ST7612AA1 #HDAC_Inhibitor #NPYM #Prodrug #ADC #self_immolative_spacer #medicinalchemistry #drugdesign https://lnkd.in/eyGW663s (Open Access Article)
A novel bioresponsive self-immolative spacer based on aza-quinone methide reactivity for the controlled release of thiols, phenols, amines, sulfonamides or amides
pubs.rsc.org
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Covalent Fragment Screening with Chemoproteomics: KEAP1 Engagers with an Unusual Warhead | https://lnkd.in/guGH2i2g Nrf2/KEAP1 modulation has been a hotly pursued pathway since the 2012 report that dimethyl fumarate and its metabolite monomethyl fumarate protect CNS neurons via up-regulation of Nrf2-dependent activities. Compounds with greater selectivity than dimethyl fumarate have been sought after for many years, culminating with a recent approval for a reversible covalent KEAP1 inhibitor and Nrf2 activator, omaveloxolone. David Weinstein, the VP and Head of Chemistry at Vividion Therapeutics, Inc. recently disclosed their efforts to identify a selective covalent KEAP1 inhibitor, VVD-702, which is active in various in vivo settings. This article highlights key aspects of this ACS Spring 2024 disclosure, which is an excellent case study for covalent hit finding using chemoproteomics, covalent compound optimization, and the use of an uncommon but surprisingly stable covalent warhead. Article | https://lnkd.in/guGH2i2g
Covalent Fragment Screening with Chemoproteomics: KEAP1 Engagers with an Unusual Warhead
drughunter.com
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Ph.D. Student @UofT Economics | Labour Economics | Medical & Health Economics | Pharmacoeconomics | Ex-JHU/JHHS/JHM | COVID-19 Command | Logistics Planning | Data Science | Lean Six Sigma | Operations
2moThoughts: GRACE definitely nailed it, getting the majority vote of support. Though HYT pushed the boundaries of equity and evLY is easy-to-apply, GRACE captures the severity adjustment intuitively with strong theory support. It was the spotlight session of ISPOR!