Drug Hunter, Palo Alto, CA (2026)

07/21/2026

Rocket Fuel-Derived Nibrozetone, a Unique Molecule with Potential Applications in Oncology and Beyond | https://drughunters.com/45dfLun

Nibrozetone (RRx-001), a molecule identified via a phenotypic screen of compounds from the rocket fuel industry, has been advanced by EpicentRx into multiple clinical trials in SCLC.

The molecule additionally received an FDA Fast Track designation for the treatment of chemotherapy-related oral mucositis in 2022 and is being studied preclinically across a variety of other indications, including outside oncology.

Structurally remarkable as a small molecule therapeutic, nibrozetone’s complex pharmacology, mechanism(s) of action, and potential therapeutic applications are still being investigated by academia and industry alike, almost 20 years after the initiation of Ph. 1 trials.

How this unconventional molecule could impact oncology, neurodegenerative disease, and targeted drug delivery will be worth monitoring.

Read more on Drug Hunter: https://drughunters.com/45dfLun

07/20/2026

Chemical Rewiring of Biological Circuits for Cancer Therapy
https://drughunters.com/4ytpgTE
Thursday, September 24th, 2026
8 AM PT | 11 AM ET | 5 PM CET

Targeted protein degradation has emerged as a powerful therapeutic approach that enables the selective elimination of disease-causing proteins by inducing proximity between a target protein and an E3 ubiquitin ligase. While heterobifunctional PROTACs and molecular glue degraders have expanded the druggable proteome and achieved regulatory approval, growing evidence suggests that these proximity-inducing modalities can offer far more than protein elimination.

In this Flash Talk, Georg Winter, Group Leader at the AITHYRA Institute for Biomedical AI, will discuss the mechanisms and therapeutic potential of TPD. Georg will highlight how such approaches differ from conventional inhibition and explore the expanding repertoire of proximity-inducing degradation strategies. The talk will also highlight emerging concepts beyond loss-of-function, including drug-induced dominant-negative effects and neomorphic pharmacology that rewires, rather than inhibits, target proteins.

Register now to learn more about how to leverage induced proximity in drug discovery: https://drughunters.com/4fdRgTO

07/17/2026

The first oral PCSK9 inhibitor has been approved!

Merck’s enlicitide (Lipfendra®), a once-daily oral macrocyclic PCSK9 inhibitor, has been approved by the FDA as an adjunct to diet and exercise to reduce LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.

PCSK9 has long been considered one of the most challenging cardiovascular targets for an oral drug. By disrupting the PCSK9–LDL receptor protein–protein interaction, enlicitide (MK-0616) delivers antibody-like LDL-C lowering in a pill.
Find out why enlicitide was selected as the 2023 Drug Hunter Molecule of the Year, including:

- Why PCSK9 is such an important—and difficult—therapeutic target
- How mRNA display technology enabled the discovery of an orally active macrocycle
- Highlights from the compound’s clinical development

Read more on DrugHunter: https://drughunters.com/4fmVO9a

07/16/2026

Registration is still open!

Join Brendan Parr and Dennis Koester on July 30 for a discussion of ten standout programs from Drug Hunter's 2025 Molecules of the Year, highlighting advances in oral macrocyclic peptides, Class B GPCRs, functionally differentiated small molecules, proximity pharmacology, and other emerging approaches.

The presentation will examine the medicinal chemistry, target biology, and design strategies driving these programs, along with key insights that can inform future drug discovery efforts.

Register here: https://drughunters.com/4wKjZ8B

07/16/2026

The FDA approved Celcuity’s dual PI3K/mTOR inhibitor gedatolisib (Revtorpyk®) to be used in combination with fulvestrant to treat adults with locally advanced or metastatic breast cancer. The combination is approved for use with or without palbociclib.

Eligible patients must be HR+ (hormone receptor-positive), HER2- (human epidermal growth factor receptor 2-negative), and without a PIK3CA mutation; patients with metastatic disease must have previously been treated.
Originally discovered at Wyeth, gedatolisib was folded into Pfizer’s oncology pipeline before its outlicensing to Celcuity in 2021.

Revisit our coverage on gedatolisib from December 2025 to learn more about the compound's discovery and development, including:

- Why dual PI3K/mTOR inhibitors are being pursued clinically
- How the discovery team optimized a bis(morpholino-1,3,5-triazine) series to identify gedatolisib
- Key clinical results from the pivotal Ph. 3 VIKTORIA-1 trial

Check out the full article on Drug Hunter: https://drughunters.com/4f5V7SZ

07/13/2026

Structure-Based Drug Design | https://drughunters.com/3RuxsCz

Understanding the molecular interactions that govern protein-ligand recognition is key to the rational optimization of ligand potency.

In the final lecture of our potency module, we discuss the structural principles behind protein–ligand binding, from electrostatics and hydrogen bonding to van der Waals contacts, halogen bonds, π-stacking, and water-mediated interactions. By analyzing the geometry, energetics, and prevalence of each interaction type, we highlight how structural information can guide rational lead optimization.

Building intuition for molecular recognition and binding-pocket complementarity can help medicinal chemists generate better design hypotheses, prioritize the most promising optimization vectors, and balance affinity with selectivity and overall drug-like properties.

Happy Learning! 🎓

07/08/2026

Getting Large Molecules Into the Brain Through Transferrin Receptor-Mediated Delivery | https://drughunters.com/4wrTvIU

The BBB (blood–brain barrier) is a formidable obstacle in CNS drug discovery, especially for biologics. Endogenous transport systems such as the transferrin receptor offer a potential route for receptor-mediated delivery into the brain.

Recent advances in TfR-targeting platforms have substantially improved CNS distribution, enabling the approval of two BBB-penetrant enzyme replacement therapies for Hunter syndrome.

Drug Hunter explains what every project leader should know including:
-The unexpected issues with early approaches that were overcome
-What every project leader needs to know to consider or compete with the modality
-Why the industry is paying attention to this approach and what to look out for

Link to report: https://drughunters.com/4wrTvIU
Request Drug Hunter access: https://drughunters.com/4vkA7wq

06/30/2026

This month’s Patent Highlights spotlight emerging strategies for difficult intracellular disease biology.

Featured disclosures include:
- Dewpoint’s β-catenin condensate modulators for Wnt-driven cancers
- Merck’s tau-binding AUTACs for autophagy-mediated clearance of pathological tau
- Janssen’s BFL-1 inhibitors targeting an underexplored anti-apoptotic resistance node in hematologic malignancies

Together, they highlight the expansion of small-molecule drug discovery into condensate biology, targeted autophagy, and apoptosis-pathway resistance.

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

06/29/2026

Ligand-Based Drug Design | https://drughunters.com/3QrZNsS

Optimizing ligand affinity requires more than adding favorable interactions: It benefits from careful management of strain, geometry, and the spatial arrangement of pharmacophore elements.

In the second lecture of our potency module, we break down the components of ligand binding and the structural vectors that govern them. Understanding how modifications tune these vectors — and how strain can be swayed to your advantage — allows discovery teams to better understand evolution of the pharmacophore during hit-to-lead optimization.

By developing an awareness of energetic landscapes and interplay between vector distance and angle, we can prioritize the evaluation and synthesis of molecules most plausible to interrogate potency hypotheses.

Happy Learning! 🎓

06/26/2026

Drug Hunter’s May picks spotlight AbbVie’s brain-penetrant small molecule CD38 inhibitor from a virtual ligand screening campaign and paralog-selective p300 degrader that achieves potent antitumor activity while sparing CBP; and cipepofol, the newly FDA-approved intravenous anesthetic from Haisco Pharmaceutical Group, marking a notable regulatory milestone in general anesthesia.

Rounding out the list:

– pozdeutinurad — Sobi and Arthrosi Therapeutics’ next-generation URAT1 inhibitor posting strong Ph. 3 urate-lowering data in gout
– GSK3494245 — GSK’s kinetoplastid proteasome inhibitor that delivered an important clinical proof-of-concept for visceral leishmaniasis, even if regimen practicality remains a challenge
– gemilukast — Ono Pharmaceutical’s leukotriene receptor antagonist
– compound 1 — a monovalent degrader of SMARCA2/4 that recruits both DCAF16 and FBXO22
– YSA64 — an RBM39 degrader with activity in AML and Ewing sarcoma models
– inobrodib — CellCentric’s p300/CBP bromodomain inhibitor, whose triplet combination strategy in AML points to a new role for epigenetic therapy in stem-cell eradication
– elpipodect — Merck’s PDE10A inhibitor, a clinically sobering but mechanistically important test of non-dopaminergic antipsychotic drug discovery

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

Full article: https://drughunters.com/3SwaCuu

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