Drug Hunter, Palo Alto, CA (2026)

01/27/2026

📣 Reminder
Metabolism-Driven Drug Design: Metabolite Profiling in Medicinal Chemistry
[LINK to Sign Up]
Thursday, January 29th, 2026
8 AM PT | 11 AM ET | 5 PM CET

In this Flash Talk, Deepak Dalvie will highlight why understanding metabolism early in drug discovery is essential, showing how early metabolite profiling can identify metabolic soft spots, anticipate reactive metabolite liabilities, and define major clearance pathways.

Through different case studies, Deepak will show how integrating metabolism data into medicinal chemistry design can improve systemic exposure, extend half-life, and reduce downstream safety risks.

Register here: https://drughunters.com/4afzk8E

01/26/2026

In this Flash Talk, Nicholas Hertz presented Montara’s two-drug approach to expand the therapeutic index of CNS drugs limited by peripheral toxicities.

He presented their lead program MTX-E1, which combines everolimus, an approved mTOR inhibitor, with a novel, peripherally restricted FKBP12 blocker (MT1110) for the treatment of TSC (tuberous sclerosis complex)-associated epilepsy. This combination therapy showed broad translatability across species, with mouse and dog data demonstrating improved inhibition of mTOR signaling in the brain and mitigation of clinically relevant peripheral toxicities, including hypercholesterolemia, lymphocyte suppression, and stomatitis.

Nicholas also shared data on a second program targeting LRRK2 for the treatment of Parkinson’s disease, leveraging Montara’s BrainTAC approach. Early chemistry efforts identified highly potent, FKBP12-dependant LRRK2 inhibitors. In vivo, lead compound MT1554 achieved LRRK2 inhibition in brain, while co-dosing a peripherally restricted FKBP12 blocker reduced peripheral inhibition, leading to nearly unchanges levels of LRRK2 in mice lung.

The full Flash Talk is available on our YouTube channel now. Check it out and share it with colleagues working on CNS targets: https://drughunters.com/49Y3wEg

01/26/2026

Ligand Binding Basics | https://drughunters.com/4pPqDGG

Ligand-target binding is a key concept in drug discovery, defining how small molecules interact with protein targets.

In this lecture, we discuss the key principles of ligand binding and fundamentals for assessing enzyme inhibition. We examine why binding kinetics, thermodynamics, and mechanism of inhibition all matter for drug design.

This section also describes how affinity can be optimized through polar contacts, desolvation effects, and conformational preorganization, and the universal contribution of hydrophobicity to ligand-protein binding.

Happy Learning! 🎓

01/24/2026

2025 Molecules of the Year: Nominate! | https://drughunters.com/45p8sR8

The final Molecules of the Month for 2025 have been announced—now it’s time to nominate your favorite compounds for the 2025 Molecules of the Year!

Nominees should either have been first disclosed or had a major update in 2025 (e.g., clinical trial results, new publication, business transaction, or regulatory approval). Eligible molecules must have a published structure and, ideally, a publication describing their properties or discovery campaign.

You can nominate clinical compounds with interesting profiles, non-clinical molecules with intriguing mechanisms of action, or recently approved drugs.

Feel free to nominate a molecule from your own company, but keep in mind that you won’t be able to vote for it in the final selection.

Most importantly, have fun with it! This is a great opportunity to reflect on the incredible science in our industry and celebrate the breakthroughs that inspire us all.

Previous winners include Gilead’s HIV capsid inhibitor lenacapavir, Pfizer’s SARS-CoV-2 Mpro inhibitor nirmatrelvir, BMS’s TYK2 inhibitor deucravacitinib, Merck’s PCSK9 inhibitor MK-0616, and Vertex’s NaV1.8 inhibitor suzetrigine.

Nominate a molecule today: https://drughunters.com/45p8sR8

01/23/2026

Molecules of the Month – December 2025 | https://drughunters.com/3LKuVkY

Drug Hunter’s final picks for 2025 spotlight Johns Hopkins Medicine's orally bioavailable MRGPRX1 PAM that delivers non-opioid neuropathic pain relief in animal models; Praxis Precision Medicines, Inc.'s precision NaV inhibitor that could become the first targeted therapy for ultra-rare pediatric epilepsies; and a broad-spectrum, non-nucleoside orthoparamyxovirus polymerase inhibitor that can rescue ferrets from a lethal, measles-like disease.

Rounding out the list:
– GSK785 — GSK's bivalent BET inhibitor with a BRD2/BRD4-selective, BRD3-sparing profile, showcasing how linker engineering can dial in isoform selectivity
– romaciclib — Ryvu Therapeutics' CDK8/19 inhibitor that dismantles venetoclax resistance networks in AML and synergizes across resistant models
– UM-203 — a reversible covalent STING inhibitor that selectively shuts down cGAS–STING signaling across species, opening a new chemotype for autoinflammatory disease
– RGH-857 — Gedeon Richter Pharma GmbH's α7 nAChR PAM built on an unusual dioxo-thiadiazine scaffold with robust procognitive effects in rodent models
– compound 26 — Ventus Therapeutics’ indazole cGAS inhibitor with a finely tuned polarity / hERG / PK balance and a design story built around an underused aminoacetonitrile motif
– compound 28 — Novartis' triazole IL-17A inhibitor that exploits Gln117 plasticity and the Trp90 pocket to deliver low-nanomolar cellular potency as a potential oral alternative to secukinumab
– compound 22 — AstraZeneca's spirocyclopentane ghrelin receptor agonist that cleanly boosts GH/IGF-1 in vivo for muscle wasting

Read the full article to explore the molecules that made our December 2025 list.

Read it on Drug Hunter: https://drughunters.com/3LKuVkY

01/22/2026

2025 Novel Small Molecule FDA Drug Approvals | https://drughunters.com/4pMrY0Z

2025 closed with 46 novel FDA drug approvals (down from 50 in 2024 and 55 in 2023). Small molecules again led the year: 32 of 46 approvals (70%), spanning multiple therapeutic areas with a clear tilt toward precision oncology.

NSCLC stood out in particular, with several approvals focused on genomically defined subtypes, another signal that biomarker-guided development continues to shape regulatory outcomes.

Outside oncology, 2025 also delivered first-in-class anti-infectives aimed at resistant pathogens, a first-in-class non-opioid NaV1.8 inhibitor for acute pain, and an expanding momentum for reversible covalent kinase inhibitors beyond cancer.

In our year-in-review, we cover the 2025 small molecule approvals, the pivotal clinical data behind them, and a poster compiling structures, mechanisms of action, dosing, and indications.

Check out the full Open Access article on Drug Hunter: https://drughunters.com/4pMrY0Z

01/21/2026

Menin Inhibitor Ziftomenib Wins FDA Approval as Monotherapy for AML | https://drughunters.com/4sSJ93J

Ziftomenib (Komzifti®), an oral menin inhibitor, was FDA approved in November 2025 for adults with relapsed/refractory AML harboring a susceptible NPM1-mutation.

The compound inhibits the key menin-KMT2A PPI, disrupting downstream transcriptional programs which promote leukemic differentiation. Discovered at the University of Michigan, ziftomenib emerged from an HTS campaign and was optimized through structure-guided medicinal chemistry.

In the KOMET-001 Ph 1/2 trial, 600 mg PO QD ziftomenib led to complete remission in 22% of relapsed or refractory NPM1-mutant AML patients; its approval comes with a boxed warning for differentiation syndrome.

Ziftomenib continues to be studied in additional adult and pediatric trials, including as a combination therapy with Bcl-2 inhibitor venetoclax and hypomethylating agent azacitidine.

Read more on Drug Hunter: https://drughunters.com/4sSJ93J

01/21/2026

Discovery of FOG-001, a Clinical Stage Helicon Inhibitor of the Beta-Catenin/TCF4 Interaction
https://drughunters.com/3LWVnYw
Thursday, February 26th, 2026
8 AM PT | 11 AM ET | 5 PM CET

Despite its central role as an oncogenic driver, β-catenin has long been considered undruggable due to its intracellular localization and limited small molecule binding opportunities.

In this Flash Talk, Brian White, Senior Director at Medicines, will present the drug discovery story of zolucatetide (FOG-001), a first-in-class, IV-dosed, stapled α-helix peptide designed to inhibit the β-catenin/TCF4 protein-protein interaction, currently advancing in Ph. 1/2 clinical trials for Wnt-driven cancers.

Brian will discuss the key preclinical data supporting candidate selection, with a focus on how backbone cyclization and unnatural amino acids enable high affinity binding, weekly dosing, and robust in vivo efficacy.

Register here to learn more about the latest advancements in stapled peptides and β-catenin-targeted molecules: https://drughunters.com/3LWVnYw

01/20/2026

Next-Generation Cardiac Myosin Inhibitor Aficamten Approved for Obstructive Hypertrophic Cardiomyopathy | https://drughunters.com/3NV3PrK

Cytokinetics’ aficamten (Myqorzo®) is an oral cardiac myosin inhibitor that has been FDA approved for patients with oHCM (obstructive hypertrophic cardiomyopathy).

A next-generation, reversible, allosteric inhibitor, aficamten is designed for simplified dose-titration relative to BMS’s mavacamten (Camzyos®), boasting a shorter half-life and shallower exposure–response aimed at lowering the risk of potential DDIs.

The compound improved heart function in people with oHCM in the Ph. 3 SEQUOIA-HCM trial and had greater improvement of exercise capacity and symptoms in a head-to-head versus the beta-blocker metoprolol. The Ph. 3 ACACIA-HCM trial is ongoing for aficamten in the non-obstructive form of the disease, a potential expanded use that would set it apart from mavacamten.

Aficamten’s approval reaffirms cardiac myosin as an appropriate target for HCM, further negating the concept that modulation of signaling systems is the only reliable pharmaceutical avenue for the disease. Similarly to mavacamten, the compound does, however, come with boxed warnings for risk of heart failure, an on-target side effect that requires regular echocardiogram monitoring during treatment.

Read it on Drug Hunter: https://drughunters.com/3NV3PrK

01/19/2026

Molecular Storytelling | https://drughunters.com/4jNpCOb
Thursday, February 19th, 2026
8 AM PT | 11 AM ET | 5 PM CET

Medicinal chemistry is often described as a rational, data-driven optimization exercise. In practice, however, real discovery programs are far messier, more creative, and deeply shaped by human judgment, intuition, and experience.

In this Flash Talk, Martin Stahl, CSO of Zenith Therapeutics, will use case studies and ideas borrowed from philosophy and the history of science to show how small molecule drug discovery is about navigating evolving narratives. Each new molecule captures past learning while simultaneously reshaping the questions that guide future design.

Martin will challenge the tendency to treat compounds as isolated data points that can be tabulated. Instead, he will show how molecules form connected chains of insights, branches of a growing knowledge tree shaped by intuition, failure, serendipity, and design. He will propose new ways of visualizing and discussing medicinal chemistry while it is still in motion. Along the way, he will highlight the hidden value of “dead ends” and examine why tacit understanding that often escapes formal documentation.

You are invited to join us taking a step back and rediscovering medicinal chemistry as a creative, storytelling discipline, and to reflect on why understanding how we got here may be just as important as where we are going next: https://drughunters.com/4jNpCOb

01/16/2026

Delgocitinib, a Topical pan-JAK Inhibitor, Becomes First FDA-Approved Treatment for Chronic Hand Eczema | https://drughunters.com/3ZefiFl

In July 2025, delgocitinib (Anzupgo®), a topical pan-JAK inhibitor, gained FDA approval for the treatment of CHE (chronic hand eczema) in adults with an inadequate response to topical corticosteroids or for whom corticosteroids are not advisable.

The JAK/STAT signaling pathway has been an area of intense focus in immunology over the past two decades, with numerous small molecule JAK inhibitors gaining regulatory approval. However, on-target toxicity associated with these drugs has led to black box warnings and safety concerns.

Selective exposure of JAK inhibitors to diseased tissue has been pursued to avoid these AEs, and delogocitinib’s topical formulation has been shown to effectively treat CHE with minimal exposure to the rest of the body and an excellent safety profile.

Read it on Drug Hunter: https://drughunters.com/3ZefiFl

01/16/2026

The IP ABCs of ADCs | https://drughunters.com/3Nf4sMR
Thursday, February 12th, 2026
8 AM PT | 11 AM ET | 5 PM CET

ADCs are reshaping the oncology landscape and their multi-component architecture creates unique challenges for building and defending a strong intellectual property portfolio. As the ADC space becomes increasingly crowded, early and strategic IP planning is critical for managing freedom-to-operate risk and supporting long-term market exclusivity.

In this Flash Talk, Deborah Smith and Julia Minitti, Partners at Wilson Sonsini Goodrich & Rosati, will present a practical roadmap for navigating the evolving IP landscape surrounding ADCs. They will discuss best practices for layering patent protection across ADC components, strategies for identifying and mitigating potential blocking patents early in R&D, and the implications of recent legal developments at the USPTO, including heightened enablement and written description standards.

They will also highlight how IP strategy decisions made early in discovery and development can directly influence the long-term commercial durability and competitive positioning of ADC programs.

Join us live for insights on creating a more resilient IP strategy for ADC development.

Sign up here: https://drughunters.com/3Nf4sMR

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