Drug Hunter

A Chameleonic Allosteric Inhibitor of WRN Helicase for MSI-High and dMMR Tumors | https://lnkd.in/gfZGTn_Z Novartis' HRO761 is an oral allosteric inhibitor targeting WRN helicase for tumors exhibiting microsatellite instability (MSI) or deficient mismatch repair (dMMR) currently in a Ph. I trial. WRN has emerged as a critical synthetic lethal target in MSI cancers, which are prevalent in colorectal, gastric, endometrial, and ovarian cancers. Despite the high response rate of MSI cancers to immune checkpoint inhibitors, many patients face resistance. The notoriously challenging-to-target WRN could become the first drugged helicase following Novartis and Vividion Therapeutics, Inc.'s clinical foray into the area. Notably, many other teams are actively developing their own WRN inhibitors making this a highly competitive area to watch in the years ahead. This article details the fascinating discovery story of HRO761 and highlights the importance of selecting appropriate assays during early HTS discovery as well as transferable medicinal chemistry strategies to optimize permeability and solubility through the modulation of LipE, neutral TPSA, chameleonicity, and non-classical zwitterions. It also explores the unique X-ray structure of HRO761 bound to WRN, how it differentiates from Vividion Therapeutics, Inc.'s VVD-214, its preclinical activity, clinical status, chemical synthesis, and more! Link | https://lnkd.in/gfZGTn_Z

A Chameleonic Allosteric Inhibitor of WRN Helicase for MSI-High and dMMR Tumors | https://lnkd.in/gfZGTn_Z Novartis' HRO761 is an oral allosteric inhibitor targeting WRN helicase for tumors exhibiting microsatellite instability (MSI) or deficient mismatch repair (dMMR) currently in a Ph. I trial. WRN has emerged as a critical synthetic lethal target in MSI cancers, which are prevalent in colorectal, gastric, endometrial, and ovarian cancers. Despite the high response rate of MSI cancers to immune checkpoint inhibitors, many patients face resistance. The notoriously challenging-to-target WRN could become the first drugged helicase following Novartis and Vividion Therapeutics, Inc.'s clinical foray into the area. Notably, many other teams are actively developing their own WRN inhibitors making this a highly competitive area to watch in the years ahead. This article details the fascinating discovery story of HRO761 and highlights the importance of selecting appropriate assays during early HTS discovery as well as transferable medicinal chemistry strategies to optimize permeability and solubility through the modulation of LipE, neutral TPSA, chameleonicity, and non-classical zwitterions. It also explores the unique X-ray structure of HRO761 bound to WRN, how it differentiates from Vividion Therapeutics, Inc.'s VVD-214, its preclinical activity, clinical status, chemical synthesis, and more! Link | https://lnkd.in/gfZGTn_Z

June 2024 News Roundup: FDA Approvals, Major Deals, Obesity Research Advances, and More | https://lnkd.in/giAZm8bt We saw several FDA approvals in June, including primary biliary cholangitis and COPD treatments. The month was marked by significant multi-billion- and million-dollar deals across various therapeutic areas. Noteworthy advances in obesity therapeutics were made, with novel targets and clinical readouts for GLP-1 agonists and NLRP3 inhibitors. Alkermes and Takeda reported clinical readouts for OX2R agonists in narcolepsy, while an antimalarial drug demonstrated promise in improving symptoms of polycystic ovary syndrome (PCOS). Despite these advancements, key molecules also had notable clinical trial failures. Did you miss any key updates? Here's a recap of June 2024's most notable drug discovery news highlights! Article: https://lnkd.in/giAZm8bt

Drug Hunter Curated Molecule Database Search | https://lnkd.in/g4v6FCKW As part of our "Molecules of the Month" and "Molecule Roundup" series of articles, which bring you the most important drug discovery molecules published on each month, we have brought together our curated molecule database into a single searchable table. This tool allows you to see longer term-industry trends in therapeutic area, target selection and chemical matter to give your drug discovery project the competitive edge you've been looking for. Try it out during our free, open access period to get a taste of the insights that Drug Hunter members are able to use to solve their drug discovery challenges | https://lnkd.in/g4v6FCKW

Drug Hunter 2023 M&A Review: Part 3 - Small Molecule-Focused Deals 10-1 | https://lnkd.in/gJGtBYfD Drug Hunter has sifted through news articles, press releases, financial disclosures, SEC filings, and more to bring you a roundup of 2023’s biggest mergers and acquisitions (M&A) in the drug discovery world. Following our open access industry overview, in part 3 of this 4-part series, we bring you the top valued small molecule-focused deals opening checkbooks in 2023. From Bristol Myers Squibb's big money acquisitions of Karuna Therapeutics, Mirati Therapeutics and RayzeBio to Roche re-entering the GLP-1 space with their purchase of Carmot Therapeutics, Inc., we have in-depth coverage and analysis of the biggest small-molecule focused deals and the chemical matter and clinical results driving them. In the coming weeks, we will be providing similarly detailed coverage and analysis of the top deals centered around biologics-based assets. Read it on Drug Hunter | https://lnkd.in/gJGtBYfD

“Why Did You Leave Genentech?” Whenever I host events, a question always comes up: “Why did you leave Genentech?” It’s asked because it’s unusual. Genentech is a scientist’s dream employer - the “Google” of biotech. Talented co-workers, incredible science, fantastic pay, you name it. Why would anyone leave? To be honest, I didn’t want to. I loved working at the forefront of drug discovery surrounded by world-class scientists I admired. In fact, in 2021, I was seriously considering shutting down Drug Hunter to focus on my increasing responsibilities. My wife had just gone through her second C-section, we had our hands full with two kids and two jobs, and I had a new project I was excited to pitch to enter the R&D portfolio. I didn’t have the evenings and weekends anymore for the full-time job Drug Hunter was turning into. My wife’s parents, John and Carol, had come down to stay with us and help with the kids since Jennie could barely walk up the stairs after her surgery. One afternoon, I was on a video call for work when my wife interrupted. “Mom and dad were in an accident.” John and Carol were on their way to pick up my daughter from daycare when a kid smashed into their stopped car at 55 MPH. Eight broken vertebrae, broken ribs, and head injuries - we were lucky they had taken our brand new SUV rather than our Corolla, or they probably wouldn’t be alive. We were so lucky our daughter wasn’t in the back seat. It’s moments like that that make you realize how precious life is and how SHORT our time here is. It was CHAOS - taking care of three incapacitated adults, a three-week-old infant, a toddler, and two dogs in a tiny rented condo, it was the first time I had ever taken real personal time off of work. It made me stop and seriously think about what I needed to do. I thought about how we were living in the Bay Area away from our families in Oregon and Michigan. I also thought about why I was giving up on Drug Hunter rather than working on it full-time, to grow it into the universal resource I had always wanted it to be. The truth was I was terrified to work on Drug Hunter, because I had no idea how it would work and if I failed, no one in the industry would ever hire me again. (In hindsight, this fear was overblown for a million reasons but that’s an entire post for another time…) I realized that was a really dumb reason not to try. If I got hit by a car the next day, Genentech would survive without me. But I would always regret not giving this "passion project" a chance. So a few months later we packed it up and moved to Oregon to live a drive away from John and Carol. I put my savings into Drug Hunter and found some angel investors to get Drug Hunter off the ground, and here we are. I always wanted Drug Hunter to become the resource I never had when I was working in drug discovery. Now I get to work every day to help everyone else turn their molecules into medicines. Three years later, I’ve never looked back! -DH

I'd vote for this if I had a vote! We propose that a Nobel Prize in Physiology or Medicine should be awarded for property-based drug design, with Christopher A. Lipinski, Paul D. Leeson, and Frank Lovering as the proposed recipients for their development of “important principles for drug design”, principles that have contributed to the development of numerous approved drugs https://lnkd.in/egs6aiW7 https://lnkd.in/eg9zCCEr

We are thrilled to announce that our guest editorial in the Journal of Medicinal Chemistry is now available online. Read our perspective why "Property-Based Drug Design Merits a Nobel Prize" here: https://lnkd.in/g3sftr4i

May 2024 Patent Highlights: STING antagonists, WIZ degraders, macrocyclic amine-based OX2R modulators, and More! | https://lnkd.in/g5hgKycB From STING antagonists to RNA degraders, our latest patent review at Drug Hunter showcases a diverse array of promising targets that are captivating drug hunters' interest. To help you quickly scan the patent literature, we’ve distilled down thousands of new documents into a searchable table of over 200 selected patents focused on key areas in drug discovery, all published in May 2024. This resource includes hand-crafted patent highlights featuring Novartis' WIZ degraders, Boehringer Ingelheim's STING antagonists, Vertex Pharmaceuticals' macrocyclic amine-based OX2R modulators, Denali Therapeutics' TMEM175 modulators, and more! Full article: https://lnkd.in/g5hgKycB

Design Principles in the Beyond Rule of 5 Space | https://lnkd.in/gi5Cr2P4 Thursday, July 11 8:00 am PDT // 11:00 am EDT // 5:00 pm CEST Modern drug discovery is now capable of targeting previously considered undruggable targets. The complexity of medicines is increasing, with many drug molecules and modalities violating at least one of Lipinski's Rule of 5 (Ro5) parameters. In the "beyond Rule of 5" (bRo5) space, unique design principles are essential. Optimizing permeability and lipophilicity is particularly challenging due to their typical anti-correlation. In this Flash Talk, Henrik Möbitz will discuss design principles in the bRo5 space. As a computational chemist, he is an expert in navigating bRo5 chemical space using physics-based computation. Henrik will explain how an analysis revealed that 3D PSA and logP thresholds of oral Ro5 and bRo5 candidates coincide. He will introduce neutral TPSA as a new parameter for lead optimization in bRo5 drug campaigns and demonstrate its optimization across four first-in-class campaigns, which led to clinical candidates or approved drugs. Notably, Henrik led the medicinal chemistry team that discovered the first-in-class WRN inhibitor, HRO761. Don't miss the chance to ask Henrik questions on bRo5 design principles. Register for his Flash Talk here: https://lnkd.in/gi5Cr2P4