Drug Hunter’s Post

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

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

August Deals and Funding Round Recap | https://lnkd.in/gfFEBHm3 In case you missed August’s business news, here’s a quick recap of five headlines, including an acquisition, three funding rounds, and a notable company closure. Article link: https://lnkd.in/gfFEBHm3