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10/20/2026

𝗦𝗲𝗿𝗲𝗻𝗱𝗶𝗽𝗶𝘁𝗼𝘂𝘀 𝗦𝗶𝗱𝗲 𝗣𝗿𝗼𝗱𝘂𝗰𝘁 𝗟𝗲𝗮𝗱𝘀 𝘁𝗼 𝗡𝗼𝘃𝗮𝗿𝘁𝗶𝘀’ 𝗦𝗲𝗰𝗼𝗻𝗱-𝗚𝗲𝗻𝗲𝗿𝗮𝘁𝗶𝗼𝗻 𝗜𝗞𝗭𝗙𝟮/𝟰 𝗗𝗲𝗴𝗿𝗮𝗱𝗲𝗿 𝗡𝗩𝗣-𝗞𝗙𝗔𝟭𝟭𝟱
In search of a second-generation IKZF2/4 degrader that could overcome the cardiotoxicity liabilities of NVP-DKY709, Novartis researchers’ diligent synthetic efforts identified a serendipitous ligand-coupled side product that changed the direction of the program.

As revealed by Simone Bonazzi at the ACS Fall 2026 First Time Disclosures session, the effort was motivated in part by clinically observed QT interval prolongation with NVP-DKY709. Because the liability could not be readily explained by hERG or other cardiac ion-channel inhibition, the team incorporated a human-induced pluripotent stem cell cardiomyocyte microelectrode array assay to capture a more physiologically integrated cardiac response.

Optimization of the serendipitous side product ultimately delivered NVP-KFA115, with improved degradation potency, permeability, and predicted arrhythmic profile.

Although the molecule was discontinued for apparent business reasons early in 2026, NVP-KFA115’s discovery story highlights both the value of emerging approaches to early cardiotoxicity monitoring and the role that persistence—and serendipity—can play in medicinal chemistry.

Read the full article on Drug Hunter: https://drughunters.com/4hQKqoK

10/19/2026

We asked members what they love about Drug Hunter.

While we heard about the importance of Drug Hunter’s data and insights, another common theme was the sense of community Drug Hunter provides, and the reminder that across companies and roles, everyone in this field is working toward the same goal.

Thank you to David Thaisrivongs (Merck), Peter Tummino (Nimbus Therapeutics), and Deborah Smith (Wilson Sonsini) for sharing!

10/18/2026

Reminder: Live Flash Talk this Thursday👇

𝗟𝗲𝘃𝗲𝗿𝗮𝗴𝗶𝗻𝗴 𝗣𝗹𝗮𝘁𝗳𝗼𝗿𝗺 𝗜𝗻𝗻𝗼𝘃𝗮𝘁𝗶𝗼𝗻 𝘁𝗼 𝗧𝗮𝗰𝗸𝗹𝗲 𝗧𝗼𝘂𝗴𝗵 𝗧𝗮𝗿𝗴𝗲𝘁𝘀

🗓️ Thursday, Oct. 22th
⏰ 8 AM PT | 11 AM ET | 5 PM CET

Drug discovery is increasingly focused on biological targets once considered undruggable. In this difficult-to-drug space, success depends on understanding how the target should be modulated, identifying molecules capable of delivering the desired mechanism, and rapidly establishing confidence in their activity.

In this Flash Talk, Andrea Weston, Head of Discovery Biology and Pharmacology at Pfizer, will explore how the thoughtful integration of platform technologies can improve the probability of success against challenging targets. She will highlight how the right protein reagents and cellular models can be critical to successful lead identification, and how defining the desired mechanism of action before screening can better position programs for success. Andrea will also examine current hit-finding strategies and emerging approaches for elucidating small-molecule MoAs, sharing how these advances are collectively expanding the boundaries of druggability and creating new opportunities to discover transformative medicines.

🔗 Register now to learn more about recent advances in platform technologies and their applications towards difficult-to-drug targets: https://drughunters.com/3U3qvcR

10/17/2026

UCB6492 Brings the Furazan Back to Oral IL-17A Inhibition | https://drughunters.com/4hOwqvJ

UCB6492 is an IL-17A inhibitor in preclinical development for inflammatory diseases. Disclosed for the first time at the EFMC International Symposium on Medicinal Chemistry 2026, UCB6492 joins a growing wave of small molecule IL-17 inhibitors aiming to challenge the efficacy benchmark established by biologics such as secukinumab (Cosentyx®).

Check out our full coverage on UCB6492 to learn how the UCB team resolved discrepancies between in vitro and in vivo toxicity findings, optimized a fragment-derived series into a development candidate, leveraged a non-classical hydrogen bond donor, and revisited the potential liability of the furazan motif.

Read more on Drug Hunter: https://drughunters.com/4hOwqvJ

10/16/2026

Targeting SHOC2 as an Emerging Approach to RAS-Driven Cancers | https://drughunters.com/4dBTf37

RAS inhibition could leave potential reactivation of the MAPK pathway through the SHOC2–MRAS–PP1C complex. Genetic dependency makes SHOC2 an increasingly intriguing target for suppressing MAPK reactivation. Tool compounds from Novartis show that the difficult PPI surface of SHOC2-RAS can be drugged.

Read more on Drug Hunter: https://drughunters.com/4dBTf37

10/15/2026

Notable Patent Structures are now live in Drug Hunter's Curated Patents feed!

Who has time to open every new patent filing each week?

Now, the Curated Patents feed allows you to quickly scan each week’s notable new patent filings to stay current on what the industry is working on.

You can now:

• 𝗦𝗰𝗮𝗻 𝗻𝗲𝘄 𝗿𝗲𝗹𝗲𝗮𝘀𝗲𝘀 𝗯𝘆 𝘀𝘁𝗿𝘂𝗰𝘁𝘂𝗿𝗲. See example structures alongside company, target, relevant therapeutic area, and individual patent data annotations.

• 𝗦𝗸𝗶𝗽 𝗠𝗮𝗿𝗸𝘂𝘀𝗵 𝗲𝘆𝗲𝘀𝗼𝗿𝗲𝘀. See specific example compounds validated by Ph.D. scientists to get a quick sense of the chemical matter.

• 𝗦𝘁𝗮𝘆 𝗰𝘂𝗿𝗿𝗲𝗻𝘁 𝘄𝗶𝘁𝗵 𝘁𝗵𝗲 𝗯𝗿𝗼𝗮𝗱𝗲𝗿 𝗶𝗻𝗱𝘂𝘀𝘁𝗿𝘆. We triage filings so that you can tune out the noise and quickly understand disclosures from across the industry outside of your main focus area.

• 𝗚𝗼 𝗱𝗲𝗲𝗽𝗲𝗿 𝘄𝗶𝘁𝗵 𝗠𝗼𝗹𝗲𝗰𝘂𝗹𝗲 𝗦𝗲𝗮𝗿𝗰𝗵. Copy/paste any SMILES into Molecule Search and edit it to find related clinical compounds, FDA approvals, and disclosures.

Already a Drug Hunter member? Log in and navigate to Patents!

Think this tool would help your team? Read more about Drug Hunter’s Curated Patents here: https://drughunters.com/480eckQ

10/13/2026

PF-07905428 Revisits Topical ACC Inhibition for Acne | https://drughunters.com/4ygseK4

PF-07905428 is Pfizer’s topical ACC (acetyl-CoA carboxylase) inhibitor developed for acne vulgaris and disclosed at the ACS Fall 2026 First Time Disclosures session.

ACC inhibition offers a direct way to suppress DNL (de novo lipogenesis) and sebum production, but earlier oral programs were limited by unexpected on-target toxicity, and previous topical approaches struggled to deliver sufficient efficacy. For PF-07905428, Pfizer designed around the specific requirements of topical delivery, using skin-flux studies to optimize physicochemical properties while incorporating high systemic clearance to limit pharmacology outside the skin.

The program provides useful lessons in balancing skin pe*******on, local target engagement, and systemic exposure in topical drug discovery, despite being discontinued after a completed Ph. 1 trial.

Check out our coverage to learn more about the discovery strategy behind PF-07905428 and Pfizer’s return to ACC inhibition for acne.

Read more on Drug Hunter: https://drughunters.com/4ygseK4

10/12/2026

Reminder: Live Flash Talk this Thursday👇

The Sulfoximine Paradox: Understanding the Unique Physicochemical Properties of Secondary Sulfonamide Bioisosteres
https://drughunters.com/4jPFC47

🗓️ Thursday, Oct. 15th
⏰ 8 AM PT | 11 AM ET | 5 PM CET

Secondary sulfonamides occur in approved medicines at a far lower rate than in screening libraries. This highlights the potential for isosteres that could achieve similar interactions but with distinct properties.

In this Thursday's Flash Talk, Michael Shultz, Director in Global Discovery Chemistry at Novartis, will discuss the unique properties of sulfoximines as secondary sulfonamide isosteres. In particular, he will present the observed differences in properties such as aqueous solubility and plasma protein binding, using MMP analysis, highlighting where values like predicted logP or fu fall short.

🔗 Register now to learn more about the sulfoximine paradox: https://drughunters.com/4jPFC47

10/10/2026

Dual JAK1/TYK2 Inhibitor Brepocitinib Finds Success in Rare Autoimmune Disease | https://drughunters.com/4ybk5X4

Brepocitinib, Pfizer/Priovant Therapeutics’ dual JAK1/TYK2 inhibitor, has been FDA-approved as the first oral treatment of the rare inflammatory disease dermatomyositis. After its initial development as a candidate therapy for several major autoimmune diseases, brepocitinib was repositioned to focus on several rare immune disorders, including dermatomyositis, where it has had clinical success.

Check out our recent coverage of brepocitinib’s development to learn the therapeutic strategy behind dual inhibition of JAK1 and TYK2, and selectivity over JAK2/3; results from evaluation in major autoimmune diseases before it was strategically re-aligned to focus on several rare immune-mediated disorders; and key results from the Ph. 3 VALOR trial that enabled the approval.

Read more on Drug Hunter: https://drughunters.com/4ybk5X4

10/09/2026

Targeting ARID1B by Converting Binders Into Degraders | https://drughunters.com/3VWHsGw

ARID1B presents a synthetic lethal vulnerability in ARID1A-mutated cancers, but its size, disorder, and lack of conventional ligandable sites make it a challenging drug discovery target. Foghorn Therapeutics’ work shows how detailed characterization of ternary complex formation and degradation kinetics can turn weak binders into selective, cellularly active degraders. This discovery strategy for FHT-654 to degrade ARID1B is a useful approach for tackling difficult targets.

Read more on Drug Hunter: https://drughunters.com/3VWHsGw

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