Drug Hunter

An Oral, Small Molecule GLP-1R Agonist Fast-Follower from Structure Therapeutics | https://lnkd.in/g5J-tsdY The recently released WHO INN proposed names list includes the structure and name of Structure Therapeutics' oral small molecule GLP-1R agonist, aleniglipron (GSBR-1290). Seemingly emerging from a “fast-follower” program based on @Chugai / Eli Lilly and Company's orforglipron, the compound includes an unusual phosphine oxide motif and has shown positive results on plasma glucose levels and bodyweight in a Ph. IIa study. Read it on Drug hunter | https://lnkd.in/g5J-tsdY

An Oral Benzothiophene BDK Inhibitor Disclosed by Pfizer | https://lnkd.in/ga83wRFc As part of our ongoing ACS Fall 2024 FTD coverage, we present the structure and discovery story of Pfizer's oral small molecule BDK inhibitor, PF-07328948. Starting from a remarkably simple thiophene carboxylic acid-based hit, which targets an allosteric pocket on BDK, the Pfizer team tackled multiple challenges, including IADRs (idiosyncratic adverse drug reactions). PF-07328948's unexpected in vivo mechanism of action and the other insights which propelled PF-07328948 into the clinic for CV indications are all in our article on Drug Hunter. Read it here: https://lnkd.in/ga83wRFc

📣Reminder!🎙️🎥 Tackling MedChem Bias One Functional Group at a Time | https://lnkd.in/gPby68fV Thu, Sep 19, 2024 8 AM PDT / 11 AM EDT / 5 PM CEST Functional groups that medicinal chemists don't encounter regularly often face greater scrutiny compared to more common ones. In his Flash Talk, Gilles Ouvry will challenge these biases and present data on four uncommon functional groups that required extra convincing to gain acceptance. Don't miss Gilles' talk! He will be available for a Q&A session afterward, offering a great opportunity to get his perspective on the uncommon functional groups you have been considering for your designs. Register here: https://lnkd.in/gPby68fV

An Allosteric Pan-Mutant-Selective PI3Kα Inhibitor Without Hyperglycemia in Preclinical Models | https://lnkd.in/gu9AyiXH RLY-2608 is an oral, mutant-selective PI3Kα allosteric inhibitor from Relay Therapeutics, targeting a cryptic pocket near the ATP-binding site. Given the challenges and toxicities associated with WT PI3Kα inhibition—such as hyperglycemia and rash—there's an increasing need for next-generation, mutant-selective PI3Kα inhibitors. Relay Therapeutics recently shared promising interim data from the Phase I ReDiscover trial in patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer. Explore this case study on RLY-2608 to dive into the discovery strategy, mechanisms driving mutant selectivity, its position in the competitive landscape, preclinical activity, recent clinical developments, and more. Full Article: https://lnkd.in/gu9AyiXH

Novartis Aims for Single Dose Malaria Cure with a Novel MoA, Long-Acting Aryl SF5 Compound | https://lnkd.in/gdx-wsDH Infection with the malaria parasite, Plasmodium falciparum, is a leading cause of fatality in the tropical regions of the world, with over 240 M infections and >600 k deaths each year. Currently, over half of the world population is at risk of infection and with the rise of resistance against current treatments, the need for new antimalarials is clear. At the ACS Fall 2024 conference in Denver, CO, Novartis outlined the structure and discovery story of NVP-IWY357, a novel antimalarial that has no cross-resistance to current drugs and the potential to achieve a single-dose cure. Read our coverage to discover how Novartis solved in vitro hERG and phototox. signals and how the incorporation of an SF5 group led to a safer GLP tox profile. Read it on Drug Hunter | https://lnkd.in/gdx-wsDH

Molecules of the Month – August 2024 | https://lnkd.in/gBWTKV32 August’s Molecules of the Month include Kannalife Sciences, Inc.'s GPR55 antagonist for chemotherapy-induced neuropathic pain and Boehringer Ingelheim’s zwitterionic inhibitor of KHK for metabolic disorders. We also feature bomedemstat, Merck's irreversible LSD1 inhibitor, a small peptide inhibitor of the Fas receptor from ONL Therapeutics, and Boehringer Ingelheim's PDE4B inhibitor with the potential to treat IPF. Read the full article to find out what compounds made our August 2024 Molecules of the Month list and check out recent articles for each. Full Article: https://lnkd.in/gBWTKV32

Thank you Bayer!! Had an awesome time visiting the Bayer Wuppertal R&D site thanks to our wonderful hosts, Nicole Biber and Markus Follmann. So much interesting discussion about the future of drug discovery - everything from the value of internal libraries to the Biosecure Act which is raising eyebrows even on this continent. Had the pleasure to meet in person the inventors of several innovative drugs. So many brilliant people here and a company with a bright future even as the industry navigates a challenging period. An excellent final stop on our so far fantastic tour in Europe. Vielen Dank!! Nicole Biber, Markus Follmann, Hartmut Beck, Lisa Candish

Do you need to spruce up your library? Check out our curated table featuring a selection of some of the best books on drug discovery, as well as related topics such as pharmacology, toxicology, pharmaceutics, and biotech. While nothing can replace hands-on industry experience, a few books serve as valuable references and offer insights into the realities of drug discovery. These are useful technical resources and informative introductions to the broader field of drug discovery, beyond any single discipline. What drug discovery books are on your reading list? Full table: https://lnkd.in/dNFFNyNF

🇩🇪 Drug Hunters in Frankfurt! 🇩🇪 Guten Morgen! Happy to finally meet old and new friends in Germany for the first time in Frankfurt! While the drug discovery community is less dense in the area, there is just as much excitement about new science, targets, and modalities as anywhere else. Many thanks to Martin Bossart, María Méndez Pérez, Volker Derdau, Thomas Maier and colleagues for kindly hosting us at Sanofi. I had no idea there was so much rich pharma industry history in the area! Thanks to those who joined us for dinner as well, especially those making the trip from as far as AbbVie Ludwigshafen (Marta Pinto) and Boehringer Ingelheim (Christian Kuttruff, Alexander Haydl). We were lucky the timing worked out to be joined by Elisabetta Chiarparin from across the channel and wonderful colleagues from Merck KGaA, Darmstadt, Germany (Julien Lefranc, Alessia Gambardella, Heide Marika Düvel (née Genau), Ana Varela. Looking forward to our final stops in Ingelheim today and Bayer Wuppertal tomorrow thanks to Nicole Biber and colleagues. While many commented that there is not a "Boston-equivalent" city in Germany, there is something magical about being able to connect between growing scientific hubs in Germany, Switzerland, the UK, France, Spain, Italy, Poland and other areas with short train rides and flights. Can't wait to be back! Auf Wiedersehen!

Molecular Glue Degraders of VAV1 Exploit a Non-Canonical Degron | https://lnkd.in/gZXQi9TW Monte Rosa Therapeutics has disclosed the structures and biological activity of over 500 molecules functioning as CRBN-mediated, molecular glue degraders of VAV1. Historically, a key challenge in the field of targeted protein degradation has been the restriction of CRBN-based molecular glue degraders to proteins with canonical “G-loop” domains. Monte Rosa’s disclosure of degraders for a protein bearing a non-canonical degron suggests that the scope of molecular glue degraders may be dramatically expanded. Does this patent application include their clinical compound MRT-6160, the second to enter clinical trials from their QuEEN™ degrader platform? Check out our patent highlight to see why this space is worth watching! Full patent highlight: https://lnkd.in/gZXQi9TW