drug hunter @drughunter_com

A single-dose cure has arrived for HAT (human African trypanosomiasis). Acoziborole is a benzoxaborole, a reversibly-covalent binder of CPSF3 in Trypanosoma parasites that leaves human CPSF3 untouched. The compound cured patients in both early- and late-stage disease, differentiating itself from the other completely oral HAT regimen, fexinidazole, which is ineffective in severe stage 2 infections. Read more on Drug Hunter: drughunters.com/439VwNt

Milsaperidone (Bysanti®) was FDA approved in February 2026 for the treatment of schizophrenia in adults and for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. With a bridging package, milsaperidone reached FDA approval roughly five years after entering the clinic. Read it on Drug Hunter: drughunters.com/4ejPGz6

Ropsacitinib (PF-06826647) is a TYK2 inhibitor that reached Ph. 2 development in plaque psoriasis and hidradenitis suppurativa. Despite encouraging psoriasis data, ropsacitinib does not appear to be in active development today, while Priovant’s dual JAK1/TYK2 inhibitor brepocitinib has become the clearer priority. Read more on Drug Hunter: drughunters.com/4dJC8gc

June is Alzheimer’s & Brain Awareness Month – and the urgency around neurodegenerative diseases drug discovery has never been clearer. Two mechanistically distinct approaches are generating serious scientific momentum, and our team at Drug Hunter published in-depth analyses on both: -TREM2 Agonists in Neurodegeneration: TREM2 signaling sits at the intersection of microglial activation, synaptic pruning, and amyloid clearance. Our analysis covers the therapeutic potential, translational data, key pharmacological challenges, and the emerging competitive landscape surrounding TREM2-targeted approaches across Alzheimer’s disease and related neurodegenerative disorders. -RNA Splice Modulators in CNS: Small molecule splice modulators are moving beyond their rare disease origins. The development of orally bioavailable RNA-targeting small molecules offer an advantage over existing RNA-targeting modalities such as siRNA, antisense oligonucleotides, biologics, and gene therapy. Our analysis discusses how RNA splice modulation strategies are being applied to complex CNS indications. Both analyses are available with complimentary access following a short platform demo. Reach out or click the link below to schedule. drughunters.com/4o0yAJO #AlzheimersAwarenessMonth #Neurodegeneration #CNS #DrugDiscovery #Biotech #AlzheimersDisease

The Drug Hunter team reviews thousands of IP disclosures each month to highlight the most impactful drug discovery patents. For April 2026, we analyzed and curated a searchable dataset of the most noteworthy disclosures, offering key data, molecular insights, and therapeutic relevance. Highlighted disclosures: -1cBio: ENPP1 inhibitors for hypophosphatasia -Arrakis Therapeutics: heterobinfunctional degraders of RNA targeting CNOT9 -Kaken Pharmaceutical: Small molecule STAT6 inhibitors -Atrogi: biased β2-adrenergic receptor agonists for obesity and metabolic disease -Para: VPS4A inhibitors targeting an untapped synthetic lethality relationship Read the full article on Drug Hunter: drughunters.com/4dQLgyx

A method that enables rapid access to glutarimides has been reported in a collaboration between the Baran Lab and BMS. Glutarimides are a key motif in the TPD (targeted protein degradation) field, and an array of scaffolds beyond those based on substituted thalidomides have entered clinical trials. However, only limited reports of glutarimides bearing α-sp3 hybridized substituents have emerged. In this Chemistry Brief, we highlight a useful extension of the nickel-catalyzed cross-coupling of hydrazides pioneered by the Baran lab and its application to scaffolds relevant to heterobifunctional and molecular glue degraders. Read it on Drug Hunter: drughunters.com/4faHOB5

Amino acids are the fundamental building blocks of proteins. Their primary sequence and the chemical properties of their side chains govern protein folding, enzyme catalysis, and molecular recognition. Explore our amino acids cheat sheet, which highlights the structures and key properties of the 21 amino acids found in the human proteome as well as their relevance in protein structure. We hope this cheat sheet serves as both a valuable resource and inspiration for drug hunters at all stages of their careers. Explore the cheat sheet on Drug Hunter: drughunters.com/49rVR1u

Paclitaxel (Taxol®) is a natural product drug first FDA approved in 1992 for ovarian cancer that later became a backbone therapy across multiple cancers. Although the program was threatened by low isolation yields and the ecological burden of harvesting Pacific yew bark, a semi-synthetic route from the more readily available natural product precursor 10-deacetylbaccatin III enabled large-scale production and helped bring paclitaxel to patients. Read more on Drug Hunter: drughunters.com/4dXLqEq

Discovery of Bexobrutideg, an Oral Targeted Degrader of BTK for the Treatment of B-cell Malignancies Thursday, July 2nd, 2026 8 AM PT | 11 AM ET | 5 PM CET BTK inhibitors targeting the orthosteric site of the protein are widely used for the treatment of B-cell malignancies. Despite significant progress, the emergence of BTK inhibitor resistant mutations is a persistent therapeutic challenge. In addition, BTK promotes BCR signaling through non-enzymatic scaffolding functions. These challenges highlight the need for therapies with an alternative mechanism of action. Bexobrutideg is an orally administered heterobifunctional small molecule degrader that acts to selectively eliminate both wild-type and mutant BTK from cells via cereblon-mediated ubiquitination and proteasomal degradation. In this Flash Talk, Barbara Czako, Executive Director of Medicinal Chemistry at Nurix Therapeutics will share the discovery story, preclinical characterization and Phase 1a/b safety and efficacy data for bexobrutideg. Register now to learn more about the discovery and preclinical and clinical findings surrounding this BTK degrader: drughunters.com/4fMZ0N6

Mitochondrial uncouplers increase energy expenditure by allowing protons to cross the inner mitochondrial membrane independently of ATP synthesis. By disconnecting mitochondrial metabolism from energy storage, these compounds increase fatty acid utilization and can reduce oxidative stress, creating therapeutic opportunities in obesity, metabolic disease, and inflammatory disorders. Unlike conventional weight-loss therapies, mitochondrial uncouplers do not directly suppress appetite and may better preserve lean mass. However, clinical development has historically been limited by narrow therapeutic windows and hyperthermia-associated toxicity. Recent advances in tissue-targeted prodrugs, controlled-release formulations, and next-generation protonophore scaffolds have renewed interest in the field. In parallel, low-dose mitochondrial uncoupling has shown promising effects in preclinical models of neurodegenerative disease, suggesting potential applications beyond metabolic disorders. After decades defined by on-mechanism toxicity, a new generation of mitochondrial uncouplers is now emerging with the potential to reshape how mitochondrial metabolism is therapeutically targeted. Read more on Drug Hunter: drughunters.com/4ebXKkz

Molecules of the Month – April 2026 Find out what molecules made our April 2026 Molecules of the Month list, and check out recent articles for each. Full article: drughunters.com/4dxKJ5z

In this Flash Talk, Ciaran Seath discussed the development and application of photoproximity labeling technologies for studying protein interactions in drug discovery. Ciaran presented two applications of this technology. µMap was used to investigate treatment-resistant HER2+ breast cancer cell lines and identified galectin-1 as a resistance-associated interactor whose inhibition restored sensitivity to HER2 immunotherapy. Ciaran also described how µMAP can be leveraged to identify context dependencies with challenging to drug targets. In MYC-driven prostate cancer a µMap approach identified the kinase SLK as a cancer-specific regulator of MYC stability. Although ubiquitously expressed, SLK accumulates in the nucleus specifically in high-risk AR-negative PC3 cells, where it physically interacts with and stabilizes MYC, revealing a previously unrecognized therapeutic vulnerability that would likely remain undetected using conventional omics approaches. If you would like to learn more about photoproximity labeling technologies and their applications in drug discovery, we encourage you to explore the full seminar and the associated preprint studies: drughunters.com/42RgwbF

On May 1, 2026, Arvinas and Pfizer’s vepdegestrant (Veppanu®) crossed the FDA finish line, marking a major milestone for targeted protein degradation. Vepdegestrant’s approval is an inflection point for the field—not just for PROTACs, but for next-generation degraders and other proximity-inducing modalities. Read more on Drug Hunter: drughunters.com/4e1ctzE

Next-Gen Utrophin Modulators for DMD: Learning from Clinical Setbacks Thursday, June 25th, 2026 8 AM PT | 11 AM ET | 5 PM CET Duchenne muscular dystrophy is a severe X-linked muscle-wasting disorder caused by mutations in the dystrophin gene, for which no curative treatment currently exists. In this Flash Talk, @Angela Russell, Professor of Medicinal Chemistry in the Departments of Chemistry and Pharmacology at the @University of Oxford, will present the discovery and clinical development of ezutromid, a first-in-class small-molecule utrophin modulator identified through phenotypic screening. She will discuss the early clinical data supporting the program and the findings that ultimately led to its discontinuation. Angela will also highlight mechanistic studies identifying AhR (aryl hydrocarbon receptor) as the molecular target of ezutromid and will highlight next-generation AhR antagonists with improved properties and efficacy as well as screening strategies leading to the identification of utrophin modulators with a distinct mechanism of action. Sign up now to learn more about utrophin modulators acting through AhR antagonism for the treatment of DMD and novel MoAs for utrophin modulation: drughunters.com/49jgnRT

TNG961: An HBS1L Molecular Glue Degrader for FOCAD-Deleted Cancers Presented by Hilary Nicholson of Tango Therapeutics at the AACR Annual Meeting 2026 New Drugs on the Horizon session, TNG961 is a potential first-in-class CRBN-mediated molecular glue degrader of HBS1L for FOCAD-deleted cancers, a subset of chr9p21-deleted tumors. FOCAD loss impairs SKI complex–mediated mRNA quality control, creating dependence on the HBS1L/PELO ribosome-rescue pathway. By selectively degrading HBS1L while sparing the closely related CRBN neosubstrate GSPT1, TNG961 disrupts this compensatory pathway and triggers translational stress in FOCAD-negative cells. Preclinically, TNG961 shows ~100-fold selectivity for FOCAD-deleted vs. WT cells and induces tumor regressions in pancreatic and NSCLC xenograft models, including tumors progressing on PRMT5 inhibitor treatment. Read more: drughunters.com/3PDrONp

DACs (degrader–antibody conjugates) combine catalytic protein degraders with mAb-mediated delivery to specific cell populations. This modality has the potential to improve tolerability and expand the therapeutic window relative to both cytotoxic ADCs and unconjugated degraders. However, the physicochemical properties of some degrader payloads—particularly their size and lipophilicity—together with the need for relatively high drug-to-antibody ratios, create significant developability challenges, including a high risk of aggregation. In addition, the multistep biological cascade required for DAC activity can lead to disconnects between the potency of free versus conjugated degraders, necessitating careful, multiparameter optimization. Despite these hurdles, several DACs have shown encouraging antigen-dependent activity, and recent disclosures of SMARCA2/4-targeting DACs suggest the potential for therapies with improved tolerability margins. Read the full review: drughunters.com/4eZY7AH

ASTX295: Designing a Short-Half-Life MDM2 Antagonist to Widen the Therapeutic Window ASTX295 is an MDM2 antagonist designed with a short half-life to deliver pulsatile p53 activation while potentially avoiding the prolonged exposure that has historically contributed to hematologic toxicity in this class of drugs. Early clinical data suggest that strategy may be working, with minimal hematologic toxicity reported in Ph. 1. After completion of the study, ASTX295 was in-licensed by Mosaic Therapeutics in 2025, and a Ph. 1b/2a study in combination with olaparib is now being prepared for biomarker-selected solid tumors. We highlight the discovery and characterization of ASTX295 presented at ACSMEDI-EFMC Medicinal Chemistry Frontiers 2025. drughunters.com/3PiqeRc

Novartis Targets Cyclin E–Driven CDK4/6 Resistance with CDK2 Inhibitor NVP-ECI830 The structure of NVP-ECI830, Novartis’ oral CDK2-selective inhibitor, was revealed at the AACR 2026 New Drugs on the Horizon session. NVP-ECI830 displays high selectivity over other CDKs, single-agent efficacy in CCNE1-amplified tumor models, and enhanced activity with CDK4/6 inhibition in vivo. Interest in CDK2 has grown as preclinical studies have implicated cyclin E–CDK2 signaling as a bypass mechanism in cancers that develop resistance to standard-of-care CDK4/6 inhibitors. CDK2 may also represent a therapeutic vulnerability in tumors that overexpress cyclin E1. Several small-molecule CDK2 inhibitors have already entered the clinic, and CDK2 has also attracted attention in the targeted protein degradation field. However, no CDK2-selective modulator has yet received FDA approval. Read more on Drug Hunter: drughunters.com/4du5iyw

TRI-611: TRI-611: Targeting Resistant CNS Metastases with an ALK Molecular Glue Degrader TRI-611 represents a differentiated approach to treatment of ALK-positive NSCLC not otherwise accessible by orthosteric kinase inhibition. The CNS-penetrant, CRBN-mediated molecular glue degrader recruits a novel, non-G-loop degron distal to the orthosteric ALK site, which may help address inhibitor-driven acquired ALK mutations while preserving activity in a setting where brain metastases and limited post-TKI options remain major challenges. The FDA Fast Track-designated program is currently in Ph. 1/2 evaluation and was disclosed by Vito Palombella of TRIANA Biomedicines at the 2026 AACR New Drugs on the Horizon session. drughunters.com/4tMXrSO

Drug Hunter CEO, Dennis Hu, will host the Opening Plenary Keynote Panel at Discovery on Target 2026 in Boston. Tackling Difficult Drug Targets: A Modality-Agnostic & Technology-Nimble Approach Tuesday, September 29 | 4:50–6:05 PM Erin Davis, PhD — Vice President, Research Business Insights & Technology, Bristol Myers Squibb Ryan Potts, PhD — VP and Head, Induced Proximity Platform, Amgen John Tallarico, PhD — Global Head, Discovery Sciences, Novartis Biomedical Research Klaus Urbahns, PhD — Head, Therapeutic Modalities, Biogen Andrea Weston, PhD — Head of Discovery Biology and Pharmacology, Pfizer David Wilson, PhD — Vice President & Global Head, Oncology Chemistry & DMPK, AstraZeneca Six leaders from across the industry in one conversation about the strategy and science behind the most challenging targets. If you’re attending #BostonDOT, this is one to catch. Pre-register here: drughunters.com/4wCtS93