Drug Hunter, Palo Alto, CA (2026)

03/27/2026

Molecules of the Month – February 2026 | https://drughunters.com/3PAOBt5

Drug Hunter’s February picks spotlight obicetrapib, a highly selective CETP inhibitor from NewAmsterdam Pharma helping revive a once-troubled class with potent LDL-C lowering in heterozygous familial hypercholesterolemia; APL-4098, Apollo Therapeutics’ GCN2 inhibitor that exploits amino acid stress signaling as a metabolic vulnerability in AML; and COMP360, Compass Pathways’ synthetic psilocybin formulation, which has now delivered a second positive Ph. 3 trial in treatment-resistant depression.

Rounding out the list:

– CSN5i-3 — an orthosteric molecular glue inhibitor of the COP9 signalosome that reveals a new class of substrate-dependent enzyme antagonists
– BMS-986458 — Bristol Myers Squibb’s oral BCL6 degrader with broad preclinical lymphoma activity and a potential first-in-class shot at this transcriptional driver
– MA48 — Weill Cornell Medicine’s small molecule CAPON inhibitor that disrupts the CAPON–nNOS interaction and opens a new neurodegeneration-relevant signaling axis
– compound 68 — an RXFP2 agonist that helped validate small-molecule activation of an underexplored endocrine GPCR
– compound 20 — Bristol Myers Squibb’s orally active tris-aminotriazine TLR9 antagonist that translated selective blockade into in vivo antifibrotic biomarker effects
– lucerastat — Idorsia’s mutation-agnostic oral substrate reduction therapy for Fabry disease, now advancing with a renal pathology-focused registration strategy
– MRT-2359 — Monte Rosa Therapeutics’ GSPT1-directed molecular glue degrader showing encouraging activity in AR-mutant metastatic castration-resistant prostate cancer

Read the full article to explore the molecules that made our February 2026 list.

Read it on Drug Hunter: https://drughunters.com/3PAOBt5

03/26/2026

February 2026 Patent Highlights | https://drughunters.com/4s0aL5B

In this month’s patent highlights, we selected a few disclosures that stood out from the thousands of newly published applications we review in our weekly updated, annotated patent search table:

• New Kv7.2/7.3 activator disclosures from Jiangxi KVVIT and Biohaven
• New HSV helicase-primase inhibitor chemotypes from Assembly Biosciences
• Selective NOX4 inhibitor disclosures from Boehringer Ingelheim
• A wave of MRGPRX2 antagonist filings pointing to growing interest in mast cell-driven diseases

Together, these filings reflect continued interest across CNS, antiviral, fibrosis/redox biology, and immunology targets.

Read it on Drug Hunter: https://drughunters.com/4s0aL5B

03/25/2026

[Open Access] ACS Spring 2026 – First Time Disclosures | https://drughunters.com/3Pu9aax

The structures are here. The First Time Disclosures session at ACS Spring 2026 in Atlanta unveiled six innovative small molecules active in the clinic.

Organized by the ACS MEDI Division and chaired by H. Rachel Lagiakos, the session showcased next-generation therapeutics in oncology and pain, including:

-Biohaven Therapeutics/CISTIM Leuven – BHV-2100: a TRPM3 antagonist for pain
-Bristol Myers Squibb – BMS-986482: a CRBN-mediated pan IKZF1-4 degrader for cancer
-Genentech/Regor Therapeutics – GDC-4198: a CDK2/4 inhibitor for cancer
-Olema Oncology/Aurigene Discovery Technologies – OP-3136: a KAT6 inhibitor for cancer
-FoRx Therapeutics – FORX-428: a PARG inhibitor for cancer
-Iambic Therapeutics – IAM1363: a HER2 inhibitor for cancer

Check out the full article to learn about the science, mechanism of action, and structures for each of these new investigational drugs.

Read more: https://drughunters.com/3Pu9aax

03/24/2026

TL1A inhibition is quietly becoming one of the most competitive therapeutic classes in IBD. What began as an intriguing and genetically supported target has progressed to a competitive landscape with
multiple late-stage programs in ulcerative colitis and Crohn’s disease. This review highlights:

- The TL1A–DR3 axis as an inflammatory amplifier
- How tulisokibart and afimkibart differ in translational strategy
- The expanding landscape of next-generation mAbs

As the field matures, the central question is less about target validation and more about durability, enrichment, and positioning within an increasingly crowded biologics market.

https://drughunters.com/3NDDn6w

03/24/2026

Voting is underway for the 2025 Molecule of the Year

From oral GLP-1 agonists and pan-RAS inhibitors to PROTAC degraders and first-in-class mechanisms, this year’s nominees represent some of the most exciting advances in drug discovery.
Now it’s your turn to weigh in.

Which molecule do you think had the biggest impact in 2025?

Explore the top 10 finalists and cast your vote here: https://drughunters.com/4saUAm5

Let your voice be heard—we’re excited to see what the community chooses.

03/23/2026

Xeruborbactam: An Ultra-Broad β-Lactamase Inhibitor Enters Ph. 1 Combination Trials | https://drughunters.com/4uLtKmH

Xeruborbactam (QPX-7728) is a boronate-based ultra-broad β-lactamase inhibitor being developed to restore β-lactam antibiotic activity against drug-resistant Gram-negative infections.

Originating from a boronic acid tool series (with lessons from vaborbactam), Qpex used extensive SAR optimization to expand enzyme coverage while engineering around key chemical liabilities.

Because the parent inhibitor has limited oral exposure, an oral prodrug (QPX-7831) was designed to improve bioavailability and rapidly release xeruborbactam via serum esterases—supporting an oral-combination strategy alongside IV development.

Xeruborbactam and its oral prodrug are now in Ph. 1 combination studies with selected β-lactams.

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

03/23/2026

In this Flash Talk, Tristan Maurer suggested dose as the ultimate MPO endpoint in small molecule drug design.

Dose predictions integrate understanding of potency, target pharmacology, and PK, into a single, decision-relevant metric. Tristan highlighted that traditional “drug-likeness” heuristics and MPOs are useful but limited. Instead, he proposed a mechanistic approach that can be broken down into three components: Desired clinical outcome (efficacy-target pharmacology relationship), the 3 pillars (binding and functional changes to target and exposure at site of action), and PK (dose-exposure relationship). Mechanistic PK/PD modeling, combined with early integration of biological context, enables translation from in vitro potency to predicted human dose.

By combining these elements with machine learning-based PK predictions, he demonstrated that Pfizer’s cDose approach facilitates early, continuously updated dose predictions, helping accelerate candidate selection and improve decision-making.

If you’d like to learn more about using dose as a design endpoint and how cDose supports early decision-making, watch the full Flash Talk on our YouTube channel: https://drughunters.com/4lJkz21

03/20/2026

Imatinib, the First Targeted Kinase Inhibitor in Oncology | https://drughunters.com/4blzZWW

Imatinib (Gleevec®/Glivec®) became a landmark FDA-approved oncogenic kinase inhibitor for Philadelphia chromosome–positive CML, targeting the BCR–ABL fusion tyrosine kinase.

Its story traces back to the identification of the Philadelphia chromosome—the t(9;22) translocation that creates BCR–ABL and is found in roughly 90–95% of CML cases—one of the earliest and most influential demonstrations that a discrete genetic lesion can define a human cancer.

A pivotal development decision was that approval-enabling trials relied on cytogenetic response as a mechanistically anchored efficacy readout—speeding the feedback loop compared with waiting for overall survival.

Following its breakthrough approval in 2001, imatinib helped ignite the modern wave of kinase-targeted oncology; by November 2025, the FDA had approved the 100th small molecule kinase inhibitor, underscoring the scale of the era it helped launch.

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

03/19/2026

Thermal Stability Assays as Tools to De-Risk Discovery | https://drughunters.com/3Nu5y7O

Thermal stability assays have progressed from a niche biophysics tool to high-throughput methods capable of confirming target engagement in both biochemical and cellular settings.

In this review, we highlight approaches including biochemical DSF, label-free nanoDSF, CETSA, and proteome-wide PISA, and illustrate how they form a continuum connecting hit identification, SAR, cellular validation, and mechanism of action.

When applied thoughtfully, these assays can reveal false SAR, aggregation risks, and off-target liabilities early, helping to refine programs and improve project trajectories.

Read the full article on Drug Hunter: https://drughunters.com/3Nu5y7O

03/19/2026

We’re headed to ACS Spring 2026 in Atlanta next week!

We’ll be in the room for First Time Disclosures (March 25, 2:00 PM) — the session that offers the earliest glimpse into the next wave of clinical-stage innovation across pharma and biotech.

Expect first looks at novel small molecules, emerging modalities, and the translational science driving them forward.

As always, we’ll be publishing an open-access deep dive unpacking the molecules, mechanisms, and clinical context behind each disclosure.

Attending? Let’s connect.
Not attending? Stay tuned — we got you covered

03/18/2026

Valbenazine: The First FDA-Approved VMAT2 Inhibitor for Tardive Dyskinesia | https://drughunters.com/4rCLwWs

Valbenazine (Ingrezza®) is Neurocrine’s FDA-approved VMAT2 inhibitor for TD (tardive dyskinesia) and chorea associated with HD (Huntington’s disease).

It builds on the VMAT2-inhibitor class established by tetrabenazine (Xenazine®)—effective, but typically requiring divided daily dosing and carrying a boxed warning for depression and suicidality in HD.

In the Ph. 3 KINECT-3 trial in TD, 80 mg once daily valbenazine significantly improved AIMS scores versus placebo at 6 weeks, with psychiatric scales generally stable over the controlled study period.

Notably, valbenazine was the first FDA-approved medication for tardive dyskinesia, a drug-induced movement disorder that can occur with long-term use of antipsychotics.

Neurocrine has also explored valbenazine beyond TD/HD—including Ph. 3 KINECT-DCP in dyskinetic cerebral palsy, which did not meet primary or key secondary endpoints—a reminder that shared movement phenomenology doesn’t always translate pharmacologically.

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

03/17/2026

Zalsupindole Could Become the First Neuroplastogen Patients Safely Take at Home for MDD | https://drughunters.com/4bgzehS

Zalsupindole, a 5-HT2A receptor partial agonist from Delix Therapeutics, leads the neuroplastogen field. This compound was discovered using the psychLight platform developed in the lab of David Olson, Delix cofounder and UC Davis professor.

The aim of the platform is to identify compounds that elicit the neuropharmacological responses displayed by many psychedelics, but without the additional hallucinatory/dissociative effects that often characterize this class of molecules.

Zalsupindole’s isoDMT core appears to have bestowed it with the desired profile, and results from Ph 1/1b studies have demonstrated promise in MDD without any signs of hallucinations. Delix has announced that based on these results, the plan for a Ph. 2 trial where patients can take the drug at home has been given the green light by the FDA.

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

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