2025 was an exceptional year for the science of drug discovery. Throughout the year, Drug Hunter covered a wide range of exciting drug discovery stories showing how advances in screening technologies, structural biology, and medicinal chemistry are expanding the druggable target space for small molecules and new modalities. In case you missed these stories, here are the top 10 most popular Drug Hunter case studies published in 2025.

Drug Hunter’s Molecules of the Month for November 2025 include a once-daily non-artemisinin combo for malaria that matched Coartem in a Ph. 3 trial while tackling emerging resistance and blocking transmission; the first Factor XIa inhibitor to succeed in Ph. 3, cutting recurrent ischemic stroke risk on top of antiplatelet therapy without increasing major bleeding; and a highly selective CDK7 inhibitor. Also featured are a peripherally restricted D2 antagonist that tames GLP-1R agonist–induced nausea and vomiting without blunting central satiety; a target-anchored SMARCA2/4 degrader that co-opt...

Gepotidacin (Blujepa®) is an oral bacterial type II topoisomerase inhibitor approved for uncomplicated UTIs and gonorrhea. Gepotidacin is a dual inhibitor of bacterial DNA gyrase and topoisomerase IV, a shared target of fluoroquinolone antibiotics. The distinct binding mode and mechanism of action of gepotidacin can help it overcome fluoroquinolone resistance mechanisms, spare the gut microbiota, and potentially address safety issues associated with fluoroquinolones. Gepotidacin, along with zoliflodacin (Nuzolvence®), mark the first new approvals for gonorrhea in over 30 years.

Each month, Drug Hunter reviews thousands of IP disclosures to curate the patents and applications most likely to move the field. From our weekly updated search table, we spotlight standout filings from November 2025—claims, structures, and therapeutic relevance. This month, we highlight Captor’s CRBN-based NEK7 degraders, Daiichi Sankyo’s SF1 antagonists and SF1 heterobifunctional degraders, Kymera’s small-molecule STAT6 inhibitors, SiteOne’s NaV1.8 pain chemotypes, and Lilly’s non-peptide amylin/calcitonin receptor agonists as oral DACRA alternatives.

As part of our Flash Talk webinar series, we present a follow-up article for Angela Mackay's Flash Talk, “Targeting NLRP3: DFV890 and Beyond.” You can also check out the recording of the talk on our Drug Hunter YouTube channel. In this follow-up article, we discuss the evolution of multiple NLRP3 inhibitors for the treatment of both peripheral and neurological immune disorders.

Mirdametinib (Gomekli®) is an oral, brain-penetrant MEK1/2 inhibitor that received FDA approval in February for adults and children with NF1-PN. The approval was based on the Ph. 2b ReNeu trial, where 52% of children and 41% of adults achieved ≥20% tumor volume reduction. Among responders, more than half of patients saw >50% tumor shrinkage. Mirdametinib is the second MEK inhibitor approved for this rare disease, following selumetinib, which was first approved for pediatric NF1-PN in 2020 and expanded in 2025 to include adults.

Fenebrutinib is a reversible, non-covalent BTK inhibitor that has delivered positive results in the first readout from pivotal Ph. 3 trials in MS. These late-stage results build on Roche’s September 2024 report from the Ph. 2 FENopta trial in RMS, where 96% patients treated with fenebrutinib were relapse-free at one year and showed no change in disability over 48 weeks. Taken together, the data have been described as “unprecedented” and suggest that fenebrutinib could become a “best-in-disease” medicine as the first high-efficacy, oral treatment option for people with either RMS or PPMS.

As part of our Flash Talk webinar series, we present a PDF of Alexander Berne's & Lucas Watkins' slide deck entitled, "Patenting Strategies for Small Molecule Drugs." You can also check out the recording of the talk on our Drug Hunter YouTube channel. In this follow-up article, we discuss the fundamentals of patent law and its essential role in driving pharmaceutical innovation. We also highlight how patents align investment incentives with exclusivity and outline the key requirements for patentability, including utility, novelty, non-obviousness, as well as enablement and written description.

The Drug Hunter data team presents a curated overview of "inactive" salts used in drug products. We show a hierarchical organization of salt acid/base properties and molecular class as well as their relative usage across FDA drug approvals. Given that many small molecule drugs are formulated and dosed as salts, these data will help salt screening efforts in development candidate selection.

Gedatolisib is an intravenously administered, ATP-competitive, multi-target inhibitor of the PI3K/AKT/mTOR pathway that blocks all four class I PI3K isoforms plus mTOR, aiming for more complete pathway suppression and less compensatory feedback than single-node agents. Discovered at Wyeth and later developed by Pfizer and then Celcuity, it is in Ph. 3 trials with palbociclib and fulvestrant for HR+/HER2– advanced breast cancer, including PIK3CA-wild-type disease, and has received Breakthrough Therapy and Fast Track designations, supporting an NDA under the U.S. FDA’s RTOR program.

JNJ-8003 is an RSV (respiratory syncytial virus) RNA polymerase inhibitor in preclinical development. One of Johnson & Johnson Innovative Medicine’s second-generation non-nucleoside inhibitors, JNJ-8003’s revamped structure eliminates key metabolic soft spots while increasing potency, driven by a compound-induced binding pocket in the L protein. Although still preclinical, JNJ-8003 could be a welcome refresh in an RSV non-nucleoside pipeline that has seen prior candidates succumb to clinical attrition, and a potential future complement to today’s largely prophylactic interventions.

Disc Medicine is repurposing Roche’s GlyT1 inhibitor bitopertin to treat the rare genetic blood disease EPP (erythropoietic protoporphyria), following its failure in schizophrenia. The background of this disease, the potential of GlyT1 inhibition to control it, and the positive Ph. 2 clinical results that led to the FDA granting Disc an accelerated review with a CNPV designation are covered in this profile. Bitopertin could become the first FDA-approved oral small molecule treatment for EPP as early as December 2025.

Sevabertinib (Hyurnuo®) is an oral, mutant HER2-targeted, reversible tyrosine kinase inhibitor approved by the FDA in November 2025 for previously treated nSCLC tumors with HER2 mutations. The approval was largely based on positive Ph. 1/2 clinical data, following its previous Breakthrough Therapy and Orphan Drug designations. Sevabertinib offers a new treatment option for this genetically defined, hard-to-treat lung cancer population, which predominantly affects younger, non-smoking women.

The FDA approved imlunestrant (Inluriyo®) on September 25, 2025, for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer following prior endocrine therapy. Imlunestrant is a next-generation, brain-penetrant oral SERD and the second agent of this class to reach the market. Meanwhile, the pipeline of clinical-stage oral SERDs and other ERα-targeting modalities continues to grow, promising plenty of competition to imlunestrant and its relatives.

STAT6, once deemed undruggable, is now being targeted through protein degradation. This article highlights recent developments including Kymera’s KT‑621, a cereblon-based STAT6 degrader, that has entered Ph. 2 and has shown >95% knockdown of STAT6 as well as Th2 biomarker suppression. It also surfaces preclinical programs from Nurix, Gilead, Pfizer and the University of Michigan. STAT6 degradation marks a shift in targeting transcription factors for immune and cancer therapies.